Dept of Physiology

DEPT OF PHYSIOLOGY

Researcher : Ballard HJ

Project Title:	Interactions between vasoconstrictor and vasodilator mechanisms in the skeletal muscle vascular response to systemic hypoxia
Investigator(s):	Ballard HJ
Department:	Physiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To investigate the roles of the baroreflex, the central chemoreflex and adaptation of the peripheral chemoreflex in the variation of sympathetic outflow to the muscle during hypoxia, and the mechanism by which sympathetic nerve activation stimulates the formation of interstitial vasodilator metabolites; to investigate the roles of A1 and A2 adenosine receptors in the vascular response to sustained hypoxia, and determine whether the receptors are located on endothelium or vascular smooth muscle; to investigate the mechanisms of the interactions between the release and actions of the vasodilator substances in hypoxia; to investigate the properties and control of the specific isoenzyme of cytosolic 5' -nucleotidase isolated from skeletal muscle vascular endothelial cells.

Project Title:	Sources and actions of adenosine in exercise vasodilation of rat red or white muscle
Investigator(s):	Ballard HJ
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To determine the venous and interstitial concentrations of adenosine in red and white muscles, and evaluate the contribution of A1 and A2 receptors to the vasodilation using appropriate blockers.

Project Title:	The role of lactic acid in the regulation of ATP efflux from skeletal muscle.
Investigator(s):	Ballard HJ
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2005

Abstract:

Skeletal muscle blood flow increases by as much as 2000% during muscle contractions. It is known that the interstitial ATP concentration increases during muscle contractions, and that this ATP is converted extracellularly to adenosine, accounting for a large part of the active hyperaemia. However, it is not known how the muscle contractions give rise to the increase in interstitial ATP. Certainly ATP can not be categorised as a “metabolic waste product”: thus, this mechanism of blood flow regulation does not fit into our existing concept for metabolic autoregulation of blood flow. Previous studies have shown that either muscle contractions (which give rise to the formation of endogenous lactic acid), or the infusion of exogenous lactic acid, cause a decrease in the muscle pH and increase both the interstitial and venous adenosine: there was a strong correlation between the depression of muscle pH and the appearance of adenosine in the venous blood, with points from both the acid infusion experiments and the muscle contraction experiments falling on a single straight line. Blockade of the cellular uptake of infused lactic acid with a-cyano-4-hydroxycinnamic acid abolished the increase in adenosine output from the muscle. Taken together, these data suggest that it is the increase in intracellular lactic acid during muscle contractions that stimulates the efflux of ATP from the muscle cells, which in turn leads to the formation of adenosine extracellularly. We have performed a small number of pilot experiments, which indicated that arterial infusion of exogenous lactic acid did, indeed, increase the interstitial ATP concentration of muscle. However, the mechanism by which lactic acid stimulates the ATP efflux, and the route by which ATP leaves the cell, are unknown, although, since ATP is a charged molecule, it is highly likely that a specific carrier is involved. The predominant mechanism of ATP transport across skeletal muscle cell membranes has not been investigated previously. A number of transporters have been identified on the surface membranes of other cell types which permit the efflux of ATP from those cells: these include members of the ATP-binding cassette (ABC) family of proteins, such as the multidrug resistance-1 protein, the cystic fibrosis transmembrane conductance regulator, and P-glycoprotein, as well as other electrodiffusional pathways, such as the cAMP-stimulated anion-selective channel. Whether any of these transporters are involved in ATP efflux from skeletal muscle cells remains to be investigated. Furthermore, the mitochondrial ATP transporter or the nucleoside transporter may play a role in ATP efflux, which should also be investigated. The objectives of this study, therefore, are to determine: 1. the influence of infused lactic acid on the skeletal muscle interstitial ATP concentration 2. whether lactic acid acts at an intra- or extracellular site to stimulate ATP efflux 3. whether ATP leaves the skeletal muscle cell through one of the known ATP transporter proteins

Project Title:	Adenosine formation in vascular endothelial cells
Investigator(s):	Ballard HJ
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2006

Abstract:

The main objective of the study is to determine whether vascular endothelial cells are capable of forming adenosine intracellularly. Adenosine acts on the skeletal muscle vascular bed to induce vasodilation during both muscle contractions and systemic hypoxia. However, during muscle contractions, adenosine acts on A2 receptors on the vascular smooth muscle cells, whereas, during hypoxia, it acts mainly on A1 receptors, which are thought to be on the vascular endothelium. Our previous studies have suggested that the site of formation of adenosine may be different during muscle contractions and hypoxia: we used interstitial microdialysis to show that the concentrations of ATP, ADP, AMP and adenosine were all elevated in the interstitial space during muscle contractions. Studies of the properties of the adenosine-metabolising enzymes in a crude homogenate of muscle showed that cytosolic 5’-nucleotidase had a much lower activity than ecto 5’ -nucleotidase, confirming that adenosine was formed extracellularly from extracellular nucleotides during muscle contractions. During hypoxia, however, we found that venous adenosine was elevated, but the venous adenine nucleotides and the interstitial adenosine and adenine nucleotides remained unchanged. This suggests that, during hypoxia, adenosine may be formed by vascular endothelial cells, and that it may be formed intracellularly. If this is so, it could explain how adenosine can act on different receptors in hypoxia from those during muscle contractions. It has been shown that the expression of 5’-nucleotidase declines very rapidly in cultured cells, and so, this question can only be addressed using freshly-isolated endothelial cells. The properties of the adenosine-metabolising enzymes of fresh endothelial cells have not been studied previously. The specific aims of this project are to: 1. Isolate vascular endothelial cells from the skeletal muscle circulation 2. Examine the properties of the isolated cells to ensure the purity of the endothelial preparation 3. Separate the cytosolic and ecto forms of 5’-nucleotidase from a homogenate of freshly isolated vascular endothelial cells 4. Study the properties of the cytosolic and ecto forms of 5’-nucleotidase

List of Research Outputs

Ballard H.J., Wong J.C.H., Das R. and Fung M.L., Neonatal hypoxia protects against hypoxic adaptation pulmonary vasculature in adults, FASEB Journal. 2007, 21(6): A1288 917.12.

Le G. and Ballard H.J., Adenosine-metabolising enzymes of skeletal muscle vascular endothelial cells., FASEB Journal. 2007, 21: 586.18.

Le G. and Ballard H.J., Isolation of skeletal muscle vascular endothelial cells. , Journal of the Hong Kong College of Cardiology . 2006, 14(2): 81.

Tu J. and Ballard H.J., Increase in interstitial ATP of rat Extensor digitorum longus muscle during lactic acid infusion. , Journal of the Hong Kong College of Cardiology . 2006, 14(2): 74.

Tu J. and Ballard H.J., Increase in interstitial ATP of rat soleus muscle during lactic acid infusion., FASEB Journal. 2007, 21: 586.17.

Researcher : Bourreau JP

Project Title:	Role of cyclooxygenase in the ventricular effects of adrenomedullin: does prostacyclin contribute towards the cardiodepression in the late hypodynamic phase of septic shock?
Investigator(s):	Bourreau JP
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To measure the levels of PGI₂ by quantifying its stable hydrolysis product, 6-keto PGF_1[alpha] by EIA after stimulation with ADM and at various time-points corresponding to the biphasic inotropic effects of ADM, and to mesure the PGI₂ levels in our animal model of terminal septic shock; to observe the signal transduction pathway involved in the ventricular effects of ADM with respect to PGI₂.

Project Title:	Endothelim-dependent hyperpolarization and relaxation of vascular smooth muscle: influence of the mode of excitation-coupling of vasoconstrictors
Investigator(s):	Bourreau JP
Department:	Physiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2005

Abstract:

To test the hypothesis that expression of endothelium-dependent hyperpolarization-induced relaxation in a given vascular bed depends on the vasoconstrictor's coupling mode. We aim in the project at establishing controlled experimental conditions that will optimise the expression of endothelium-dependent hyperpolarization-induced relaxation and thus optimize the investigation of its mechanism(s).

Project Title:	Switch in G-protein coupling. Role of intracellular cAMP
Investigator(s):	Bourreau JP
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	01/2006

Abstract:

In our animal model of septic shock, we were able to identify the overproduction of the vasoactive peptide adrenomedullin as a key factor responsible for depression of ventricular function during the hypodynamic phase of shock (Am.J.Physiol., Heart Circ.Physiol. 286: H1034-H1042, 2004).Physiologically, this peptide is a positive inotropic substance that increases the force of contraction via a beta adrenergic-like effect; i.e., by raising the intracellular cAMP concentration. This triggers PKA-dependent phosphorylation of key protein targets (L-type calcium channels, phospholamban, TnC…), which results in positive inotropy and lusitropy.It was thus difficult to understand why a substance that, as often claimed in the litterature, should function to overcome situations where cardiac function is compromised (such as septic shock), failed to do so but rather contributed significantly to the progression of ventricular depression.We have also gathered data showing that the negative inotropic effect of adrenomedullin develops slowly and is dependent on the concomittent expression of the inducible form of cyclooxygenase, COX2 (Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1034-42). Moreover, our recent findings (under revision, Am J.Physiol.) show clearly that this negative inotropic effect of adrenomedullin in the presence of COX 2 induction is pertussis toxin-sensitive, suggesting a switch in G-protein coupling from Gs to Gi. This negative inotropic effect of adrenomedullin is also sensitive to inhibition of PKA, which suggests that PKA-dependent phosphorylation of specific target(s) is responsible for the switch, implicating a role for cytosolic cAMP in this phenomenon.Therefore, the model we propose assumes that it is an uncontrolled increase in cAMP, due to ADM and prostaglandins (most probably prostacyclin) stimulation that initiate a sequence of events leading to a switch in G-protein coupling between adrenomedullin receptor and cellular response. This cAMP-dependent switch would thus be the trigger for the depressant effect of adrenomedullin on the ventricule during septic shock.The goal of this project is to test this hypothesis by quantifying cAMP in rat ventricular myocytes in conditions were adrenomedullin has a positive and a negative inotropic effect, and to confirm that pharmacological manipulations of these myocytes that inhibit the effects of adrenomedullin ultimately result in a decrease production of cAMP.

Project Title:	Ventricular excitation-contraction coupling during septic shock: Influence of adrenomedullin
Investigator(s):	Bourreau JP
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To quantify the changes in cellular cAMP occurring in ventricular myocytes isolated from rats in the hypo-dynamic phase of septic shock; to quantify the effect of adrenomedullin receptor blockade (qnd/or COX II inhibition) on the cAMP levels in myocytes isolated fron shocked rats; to document the cellular pathways involved, leading to depression of ventricular myocytes twitch contraction; to identify the processes of excitation-contraction coupling in ventricular myocytes altered during the hypo-dynamic phase of septic shock, and document the implication of adrenomedullin in these changes.

List of Research Outputs

Researcher : Bruce IC

Project Title:	Biomedical writing for postgraduate students whose mother tongue is Chinese: a novel course based on interactive multimedia
Investigator(s):	Bruce IC
Department:	Physiology
Source(s) of Funding:	Teaching Development Grants
Start Date:	02/1999

Abstract:

Two tasks need to be accomplished. Firstly, how best to teach and learn the art and craft of creating a manuscript suitable for submission to an international journal. Secondly, how to develop a teaching tool that is sensitive to the specific difficulties encountered by individuals whose usual channels of communication are Chinese. The unifying strategy is to create and interactive web site that can be used, in combination with face-to-face teaching, to develop the desired writing skills and attitudes.

List of Research Outputs

Researcher : Chan CH

List of Research Outputs

Chan C.H., Kwok A.W.S., Chan Y.S., Li X. and Shum D.K.Y., Upregulation of nitrated chondroitin sulfate proteoglycans in reactive astrocytes and cerebrospinal fluid of patients with amyotrophic lateral sclerosis, Proceedings of the 4th Congress of FAONS, Nov 30 - Dec 2, Hong Kong. 2006, 108.

Researcher : Chan WH

List of Research Outputs

Chan W.H., Chung S.K. and Chung S.S.M., Contribution of polyol-pathway to slow-developing diabetic cataract, International Symposium on Healthy Aging: A Gloval Challenge for the 21st Century. 2006.

Researcher : Chan WS

List of Research Outputs

Chan W.S., Chen L., Chan Y.S. and Yung K.K., Modulation in expression of neurokinin receptor NK1 in the striatum of 6-hydroxydopamine-lesioned rats, Neurosignals. 2006, 15: 120.

Chan W.S., Chen L., Chan Y.S. and Yung K.K., Neurokinin receptor one agonist septide offers neuroprotection on dopaminergic neurons, Neurosignals. 2006, 15: 140.

Researcher : Chan YS

Project Title:	Sensitive period for topographic spatial representation in the rat otolith system
Investigator(s):	Chan YS
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2003

Abstract:

To determine whether the functional organization of a gravity-related spatial reference in the postnatal inferior olive is perturbed by perinatal blockade of the vestibular nucleus; to determine whether the spatial coding capacity of adult neurons are perturbed well after an early postnatal blockade becomes ineffective; to examine if the pharmacological manipulations applied later in the postnatal period have any effect in the mature brain.

Project Title:	The role of central glial cells in the pathogenesis of Parkinson's Disease
Investigator(s):	Chan YS
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To employ immuno-hybridization histochemical methods to map the spatiotemporal distribution of different activated glial cells during the development of PD as induced by systemic administration of a neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Project Title:	Development of commissural inhibition in the vestibular system
Investigator(s):	Chan YS
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2005

Abstract:

To map the postnatal maturation time and the location of canal-related neurons in the vestibulo-olivary pathway; to document the location and maturation profile of inhibitory neuronal correlates in the commissural otolith pathway; to examine the developmental change of inhibitory postsynaptic current (IPSC) at central GABAergic synapses in brainstem slices containing the vestibular nucleus.

Project Title:	Development of glutamate transmission and frequency responsiveness in central vestibular neurons
Investigator(s):	Chan YS
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2005

Abstract:

To examine the postnatal change of excitatory postsynaptic current at glutamate synapses in the vestibular nucleus; to investigate the frequency responsiveness of neuronal subgroups within the medial vestibular nucleus.

Project Title:	Functional maturation of excitatory and inhibitory synaptic receptors in canal-and otolith-related neurons of the inferior olive
Investigator(s):	Chan YS
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2006

Abstract:

To examine developmental change of excitatory postsynaptic currents at glutamate synapses on canal- and otolith-related inferior olivary neurons; to examine developmental change of inhibitory postsynaptic currents at GABAergic synapses on canal- and otolith-related inferior olivary neurons.

List of Research Outputs

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Intracerebral injection of granulocyte-colony stimulating factor reduces infarct volume following transient middle cerebral artery occlusion in mice, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Chan C.F., Leung A.Y.H., Chan Y.S. and Cheung R.T.F., Use of granulocyte-colony stimulating factor in a mice stroke model, 11th Research Postgraduate Symposium. 2006, 60.

Chan C.H., Kwok A.W.S., Chan Y.S., Li X. and Shum D.K.Y., Upregulation of nitrated chondroitin sulfate proteoglycans in reactive astrocytes and cerebrospinal fluid of patients with amyotrophic lateral sclerosis, Proceedings of the 4th Congress of FAONS, Nov 30 - Dec 2, Hong Kong. 2006, 108.

Chan W.S., Chen L., Chan Y.S. and Yung K.K., Modulation in expression of neurokinin receptor NK1 in the striatum of 6-hydroxydopamine-lesioned rats, Neurosignals. 2006, 15: 120.

Chan W.S., Chen L., Chan Y.S. and Yung K.K., Neurokinin receptor one agonist septide offers neuroprotection on dopaminergic neurons, Neurosignals. 2006, 15: 140.

Chan Y.S. and He J., New Perspectives in Vestibulo-Auditory Neurobiology., Neuroembryology and Aging. 2006, 3: 161.

Chan Y.S., Jiang Z.D. and Lai C.H., Pre- and postnatal development of the vestibular system. In: W.Q. Cai (Ed), Chapter 11. Science Publisher, Beijing; pp, Developmental Neurobiology. 2007, 391-403.

Chan Y.S., Lai C.H. and Shum D.K.Y., Spatial coding capacity of central otolith neurons. , Exp Brain Res. 2006, 173(2): 205-214.

Chen L.W., Zhang J.P., Shum D.K.Y. and Chan Y.S., Localization of NGF, NT3 and GDNF in nestin-expressing reactive astrocytes in the caudate-putamen of MPTP-treated C57/BL mice, Journal of Comparative Neurology. 2006, 497(6): 898-909.

Chu J.Y.S., Lee L.T., Lai S.K., Chan Y.S., Yung W.H. and Chow B.K., The hypothalamo-neurohypophsial secretinergic pathway in regulating body water homeostasis, Proceedings of the 4th Congress of FAONS. 2006, 108-109.

Gao J., Cheung R.T.F., Lee T.M.C. and Chan Y.S., Cognitive assessment in normal aging and in the early Alzheimer’s disease, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population. 2007, 57.

Gao Y.P., Li C., Wang N.Q., Sun X., Chan Y.S. and He J.F., Cortically derived highly synchronized oscillation (0.3-3 Hz) in the auditory thalamus is via the direct excitatory pathway rather than the thalamic reticular nuclei, Proceedings of the 4^th Congress of FAONS. 2006, 115.

Guo Y.P., Chan Y.S. and He J., Fos expression in the auditory thalamus is triggered by corticofugal projections, Soc. Neuroscience Abstract (U.S.A.). 2006, 543: 2.

Guo Y.P., Sun X., Li C., Wang N.Q., Chan Y.S. and He J., c-fos expression in the auditory thalamus is triggered by corticofugal projections, Proceedings of National Academy of Sciences. 2007, 104: 11802-11807.

Kwok J.C.F., Lau J.W.K., Ng K.Y., Shum D.K.Y. and Chan Y.S., Chondroitin sulfates enriched in the developing rat hindbrain restrict commissural projections of vestibular neurons, Neurosignals. 2006, 15: 123-123.

Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13.

Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4^th Congress of FAONS. 2006, 13.

Lai C.H., Tse Y.C., Shum D.K.Y. and Chan Y.S., Toward maturation of the vestibular system: neural circuits and neuronal properties, Neuroembryology and Aging. 2006, 3: 162-170.

Lai S.K., Yung W.H. and Chan Y.S., Synaptic regulation of glutamate receptor subunit composition in central vestibular neurons during neonatal development, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 13.

Lau J.W.K., Kwok J.C.F., Ng T.K., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display differential commissural projection patterns with digestion of chondroitin sulfates, Proceedings of the 4th Congress of FAONS Nov 30 - Dec 2, Hong Kong. 2006, 25.

Lee R.W.P., Lau J.W.K., Li C., Lai C.H. and Chan Y.S., Alteration in the distribution of otolith-related inferior olivary neurons after perinatal blockade of glutamate transmission in the vestibular nuclei, Proceedings of the 4th Congress of FAONS. 2006, 98.

Lee R.W.P., Tse Y.C., Sun J., Chan Y.S. and Lai C.H., Developmental expression of metabotropic glutamate receptor subtype R1a in rat vestibular nuclear neurons responding to linear accelerations., Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 9.

Lee S.M., Chan Y.S., Wang J.J., Chow B.K. and Yung W.H., Expression of secretin in the rat prenatal and postnatal cerebellum, Neurosignals. 2006, 15: 124.

Leung K.W., Yung K.K., Mak N.K., Chan Y.S., Fan T.P. and Wong N.S., Neuroprotective effects of Ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity, Neuropharmacology. 2007, 52: 827-835.

Li C., Guo Y.P., Chan Y.S. and He J., Postnatal development of corticofugal modulation in the auditory thalamus in rats, Soc. Neuroscience Abstract (U.S.A.) . 2006, 543: 1.

Li C., Liu J., Lai C.H. and Chan Y.S., Postnatal expression of glutamate receptor subunits in rat inferior olivary neurons responsive to horizontal linear acceleration, Neurosignals. 2006, 15: 125.

Liu C.H., Gao L.X., Yu Y.Q., Chan Y.S., He S.G. and He J.F., Correlation of neural oscillation between the auditory thalamus and with the brainstem input, Proceedings of the 4th Congress of FAONS. 2006, 112-113.

Liu C.H., Zhang Z., He S.G., Chan Y.S. and He J., Spindle-like oscillation in the thalamus is synchronized with the brainstem input, Soc. Neuroscience Abstract (U.S.A.). 2006, 543: 3.

Liu H., Liu J., Chan C., Chau C.H., Chan Y.S. and Shum D.K.Y., Chondroitin sulfate moieties that are upregulated in Schwann cell-astrocyte encounters, Gordon research Conference on Proteoglycans July 9-14 Andover, New Hampshire, USA. 2006.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Change in the composition of perineuronal nets of central vestibular neurons following unilateral labyrinthectomy, Congress of FAONS. 2006, 100.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in Perineuronal Nets within the Rat Vestibular Nuclei during Postnatal Development and in Injury., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 12.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Society for Neuroscience (USA) Oct 14-18 Altanta, GA, USA. 2006, 550.12.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets of rat vestibular nuclear neurons after unilateral labyrinthectomy, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P41.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets within the rat vestibular nuclei during postnatal development, Proceedings of the 29th Annual Meeting of Japan Neuroscience Society, Kyoto Japan, July19-21. 2006, PS2A-F188.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Proceedings of the 4th Congress of FAONS, Nov. 30 - Dec. 2 Hong Kong. 2006, 100.

Sun X., Xia Q., Lai C.H., Shum D.K.Y., Chan Y.S. and He J., Corticofugal modulation on acoustically induced Fos expression in the rat auditory pathway, J. Comparative Neurology. 2007, 501: 509-525.

Sun X., Chan Y.S. and He J., Expression of Fos protein in the medial geniculate body of cochlear-ablated and cortical-activated rats, Neurosignals. 2006, 15: 128-129.

Tam K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Chondroitinases ABC I and II from Proteus Vulgaris for Therapuetic Use: Cloning and Characterization., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Tam K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Recombinant expression and characterization of chondroitinse ABC I and II, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P8.

Tse Y.C., Lai S.K., Zhou H., Yung W.H. and Chan Y.S., AMPA and NMDA receptor properties in spinal vestibular neurons of developing rats, Neurosignals. 2006, 15: 143.

Tse Y.C., Zhou H., Lai C.H., Yung W.H. and Chan Y.S., Developmental profile of ionotropic glutamate receptors in the vestibular nucleus of rats: Analysis of miniature synaptic currents and c-fos expression, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 3.

Yiu C.N.S., Lai C.H. and Chan Y.S., Developmental expression of Fos protein in horizontal-canal related vestibular nuclear neurons of postnatal rat following angular acceleration, Neurosignals. 2006, 15: 132-133.

Yiu C.N.S., Chan Y.S. and Lai C.H., Developmental responsiveness of canal-related brainstem neurons to vertical head rotation, Proceedings of the 4^th Congress of FAONS. 2006, 102.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal motions, Proceedings of the 29^th Annual Meeting of Japan Neuroscience Society. 2006, PS2A-F187.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal rotational and translational motions, Neurosignals. 2006, 15: 142.

Yung W.H., Lee S.M., Chan Y.S., Wang J.J. and Chow B.K., Expression and action of secretin in rat cerebellar deep nuclei neurons, Neurosignals. 2006, 15: 118-119.

Zhang J., Yung W.H., Chow K.C., Chan Y.S. and Wang J.J., The role of secretin and cerebellum in autism, In: Wang XM, Progress in Neuroscience 4. Beijing, Higher Education Press, 2006, 482-492.

Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of heparanase in the normal versus injured spinal cord of adult rats, Soc. Neuroscience Abstract (U.S.A.). 2006, 720: 12.

Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of heparanase in the normal versus injured spinal cord of adult rats, Society for Neuroscience (USA) Oct 14-18, Altanta GA, USA. 2006, 720.12/C28.

Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Cellular localization of heparanase in the normal versus injured spinal cord of adult rats, Society for Neuroscience Abstracts (USA) Oct 14-18, Altanta GA, USA. 2006, 720.12/C28.

Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Expression patterns of heparanase in normal and injured rat spinal cord, Proceedings of the 4th Congress of FAONS. 2006, 67.

Zhang Y., Yeung M.N., Chau C.H., Chan Y.S. and Shum D.K.Y., Mapping heparanase expression in the spinal cord of adult rats, J. Comparative Neurology. 2006, 494: 345-357.

Zhang Y., Chan Y.S. and Shum D.K.Y., Molecular cloning characterization and purification of rat pro- and mature heparanase, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P11.

Zhang Y., Chau C.H., Chan Y.S. and Shum D.K.Y., Proceedings of the 4^th Congress of FAONS, Proceedings of the 4th Congress of FAONS. 2006, 67.

Zhang Z., Chan Y.S. and He J., Thalamocortical and corticothalamic interaction in the auditory system, Neuroembryology and Aging. 2006, 3: 239-248.

Zhu J.N., Yung W.H., Chow B.K.C., Chan Y.S. and Wang J.J., The cerebellar-hypothalamic circuits: potential pathways underlying cerebellar involvement in somatic-visceral interaction, Brain Research Review. 2006, 52(1): 93-106.

Researcher : Chen L

List of Research Outputs

Chan W.S., Chen L., Chan Y.S. and Yung K.K., Modulation in expression of neurokinin receptor NK1 in the striatum of 6-hydroxydopamine-lesioned rats, Neurosignals. 2006, 15: 120.

Chan W.S., Chen L., Chan Y.S. and Yung K.K., Neurokinin receptor one agonist septide offers neuroprotection on dopaminergic neurons, Neurosignals. 2006, 15: 140.

Researcher : Cheng SA

List of Research Outputs

Cheng S.A., Tam C.W., Yao K.M. and Shiu S.Y.W., The anti-proliferative effects of sPDZD2 on prostate and non-prostate cancer cells, FASEB Journal. 9650 ROCKVILLE PIKE, BETHESDA,USA, FEDERATION AMER SOC EXP BIOL, 2007, 21 (5): A387.

Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human sPDZD2 protein, 3rd PacRim Breast and Prostate Cancer Meeting, Kingfisher Bay Resort, Fraser Island, Queensland, Australia. 2006, 41.

Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor, Endocrinology. 2006, 147: 5023-5033.

Researcher : Chung SSM

Project Title:	Osmoregulation in lens
Investigator(s):	Chung SSM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Outstanding RGC Projects
Start Date:	09/1998

Abstract:

It is imperative to have a better understanding of the mechanisms leading to various cataracts such that preventive measures can be developed. Since maintaining the ionic strength and ionic composition in the lens is essential for the transparency of the lens, we plan to study the mechanism of osmoregulation in this organ. Transgenic mice that over-express aldose reductase and sodium dependent myoinositol transporter in their lenses will be used to increase the lens' level of sorbitol and myoinositol, respectively. We will determine if high level of these osmolytes causes cataract development, and see when the level of one osmolyte is high, will the lens compensate by reducing the level of other osmolytes. We will also determine whether high intracellular osmotic pressure affects the regulation of expression of genes that control the level of osmolytes such as aldose reductase, sodium dependent myoinositol transporter, and taurine transporter.

Project Title:	Effects of early postnatal feeding on fatty acid metabolism
Investigator(s):	Chung SSM, Sheng HP
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	11/2002

Abstract:

Both epidemiological studies and animal studies have shown that prenatal and early postnatal nutrition not only affects infant growth and development, it also predetermines future metabolism, performance adn morbidity. This study addresses the problems of nutritional environment during the sucking period on lipid metabolism and later-life obesity.

Project Title:	Polyol pathway in diabetic dyslipidemia
Investigator(s):	Chung SSM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2003

Abstract:

To determine if AR null mutation reduces plasma TG levels in diabetic mice; to determine if ARI reduces plasma TG in diabetic mice; to determine if AR null mutation or ARI nor ARI normalizes LDL and HDL leviabetic mice.

Project Title:	Mechanism of Nogo-A inhibition of axonal regeneration
Investigator(s):	Chung SSM, Chung SK
Department:	Institute of Molecular Biology
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	01/2003

Abstract:

To develop Nogo gene knockout mice to determine the role of this gene in the inhibition of axonal regeneration and its physiological functions; to develop transgenic mice that overexpress Nogo-A in their Schwann cells to determine if that would make their PNS non-permissive for axonal regeneraton; to develop transgenic mice that overexpress mutant Nogo-A with the Nogo-66 or aa623-640 region deleted to determine which domain is responsible for the inhibitory effect of Nogo-A.

Project Title:	The polyol pathway as a thrifty pathway promoting energy storage
Investigator(s):	Chung SSM
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2003

Abstract:

To determine the in vivo conversion of glucose to fatty acids and triglycerides in normal mice and mice deficient in AR; to determine if AR deficiency affects the activities of lipogenic/adipogenic transcriptional factors including ADD1/SREBP-1 and CHOP-C/EBP-[alpha], anti-obesity transcriptional factor FOXC2, and enzymes fatty acid synthase (FAS) and stearoyl CoA desaturase (SCD); to assess whether administration of inhibitors of aldose reductase (ARI) will affect obesity and improve glucose tolerance in the agouti yellow mice; to determine whether the effects of aldose reductase deficiency on agouti-induced lipogenesis and obesity can be duplicated in diet-induced obesity models.

Project Title:	Aldose reductase in diabetic cataract
Investigator(s):	Chung SSM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	10/2004

Abstract:

To determine if the antioxidant can prevent AR-induced slow-developing cataract; to determine the osmolyte content and oxidative status of the slow-developing cataract; to compare the morphological changes in the acute diabetic cataract and the slow developing cataract; to determine if there is apoptosis in the epithelial cells of the precataractous lenses.

List of Research Outputs

Chan W.H., Chung S.K. and Chung S.S.M., Contribution of polyol-pathway to slow-developing diabetic cataract, International Symposium on Healthy Aging: A Gloval Challenge for the 21st Century. 2006.

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Deletion of aldose reductase gene protects against neuronal death and edema in retina after transient ischemia by preventing oxidative stress, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

Chung S.K. and Chung S.S.M., Transgenic and knockout mouse models of diabetic neuropathy, The Clinical Management of Diabetic Neuropathy, Second Edition. 2007.

Chung S.S.M., Aldose reductase in diabetic retinopathy, 8th Scientific Meeting of the Association for Occular Pharmacology. 2007.

Chung S.S.M., Mechanism of polyol pathway in diabetic complications, Conference on diabetic complications 2007: role of aldose reductase and related pathways, Kona, Hawaii. 2007.

Ho H.T.B., Ko C.B., Cheung A.K.H., Lam A.K.M., Tam S., Chung S.K. and Chung S.S.M., Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice, Kidney International. 2007, 72: 63-71.

Huang P., Jiang Z., Teng S., Wong Y.C., Frohman M.A., Chung S.K. and Chung S.S.M., Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na, K-A TPase activity and osmotic stress, Experimental Eye Research. 2006, 83: 939-948.

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 11th Reserach Postgraduate symposium 2006.

Li H., Fung K.L., Jin D., Chung S.S.M., Ching Y.P., Ng I.O.L., Sze K.H., Ko C.B. and Sun H., Solution Structures, Dynamics, and Lipid-binding of the Sterile a-Motif Domain of the Deleted in Liver Cancer 2, PROTEINS: Structure, Function, and Bioinformatics. 2007, 67: 1154-1166.

Lo A.C.Y., Hung K.L., Cheung K.H.A., He Q., Chiu J., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from iron- and transferrin-related oxidative stress and cerebral ischemic injury, 36th Annual Meeting of the Society for Neuroscience 2006.

Mak M.C., Lo A.C.Y., Lam A.K.M., Chung S.S.M. and Chung S.K., NFAT5 deficiency increases the severity of neuronal cell death in ischemic , 36th Annual Meeting of the Society for Neuroscience 2006.

Tong E.H.Y., Guo J.J., Huang A.L., Liu H., Hu C.D., Chung S.S.M. and Ko C.B., Regulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5, Journal of Biological Chemistry. 2006, 281: 23870-23879.

Yamagishi S.I., Ogasawara S., Sugawara A., Chung S.S.M., Chung S.K. and Yagihashi S., Glycemic control is crucial for the treatment of aldose reductase inhibitor (ARI), Lessons from Diabetic AR-deficient Mice, Hawaii. 2007.

Yang J.Y., Tam W.Y., Tam S., Guo H., Wu X., Li G., Chau J.F., Klein J.D., Chung S.K., Sands J.M. and Chung S.S.M., Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism, American Journal of Physiology Renal Physiology. 2006, 291: F186-F195.

Researcher : Das R

List of Research Outputs

Ballard H.J., Wong J.C.H., Das R. and Fung M.L., Neonatal hypoxia protects against hypoxic adaptation pulmonary vasculature in adults, FASEB Journal. 2007, 21(6): A1288 917.12.

Researcher : Fung ML

Project Title:	Renin-angiotensin system in the carotid body: its expression and functional implications in intermittent hypoxia
Investigator(s):	Fung ML, Tipoe GL, Leung PS
Department:	Physiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	07/2006

Abstract:

I quoted the project objectives and long term impact of the "fundable but not funded" CERG project entitled: "Renin-angiotensin system in the carotid body: its expression and functional implications in intermittent hypoxia " submitted in last RGC exercise:"The long-term objective is to delineate (1) the physiological mechanisms underlying the modulation of carotid chemoreceptor functions and (2) the pathophysiological pathways by which mediate changes in the cardiopulmonary activities during intermittent hypoxia (IH). Chemoreceptors in the carotid body are central to the cardiopulmonary responses to acute hypoxia, and the carotid body plays an important role in the pathogenic events in IH. We have recently shown the expression of functional angiotensin II receptors (AT1) in the chemosensitive cells and a local renin-angiotensin system (RAS) in the carotid body. These data prompt us to propose the following specific aims for examining the general hypothesis that the RAS in the carotid body plays an important role in the modulation of carotid chemoreceptor activity in IH.Specific aim 1 is to determine the effect of IH on the gene expression of RAS in the carotid body. Specific hypothesis 1 is that the expression of RAS is upregulated in the carotid body with IH compared with those of the normoxic control and continuous hypoxia (CH). .Specific aim 2 is to determine the functional changes associated with the RAS expression in the carotid body in IH. Specific hypothesis 2 is that increased expression of ACE and AT1 receptors in IH carotid body enhances ACE activity, the [Ca++]i response to angiotensin II (AngII) in the glomus cells and the afferent nerve activity in the chemoreceptor. "

Project Title:	Renin-angiotensin system in the carotid body: its expression and functional implications in intermittent hypoxia
Investigator(s):	Fung ML, Tipoe GL
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To determine the effect of intermittent hypoxia (IH) on the gene expression of RAS in the carotid body; to determine the functional changes associated with the RAS expression in the carotid body in IH; to determine the effect of IH on the expression and function of AT₄ receptor in the carotid body.

List of Research Outputs

Ballard H.J., Wong J.C.H., Das R. and Fung M.L., Neonatal hypoxia protects against hypoxic adaptation pulmonary vasculature in adults, FASEB Journal. 2007, 21(6): A1288 917.12.

Fung M.L., Lam S.S.Y., Wong T.P., Tjong Y.W. and Leung P.S., Carotid body AT₄ receptor expression and its upregulation in chronic hypoxia, The Open Cardiovascular Medicine Journal. 2007, 1: 1-7.

Fung M.L., Editorial Board Member, Open Biochemistry Journal. Bentham Science Publishers Ltd., 2007.

Fung M.L., Editorial Board Member, Open Cardiovascular Medicine Journal. Bentham Science Publishers Ltd., 2007.

Fung M.L., Guest Editor, In: M. L. Fung and T. M. Wong, Drug Targets - Cardiovascular and Hematological Disorders. Bentham Science Publishers Ltd., 2007, 7(2).

Fung M.L., Li M. and Lahiri S., Increased endogenous nitric oxide release by iron chelation and purinergic activation in the rat carotid body, The Open Biochemistry Journal. 2007, 1: 1-6.

Fung M.L. and Wong T.M., Metabolic syndrome in an Asian population and agents and targets for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 77-78.

Fung M.L., Tjong Y.W., Hung M.W. and Li M., NO problem with sleep apnea? (Hong Kong-Taiwan) Taipei, The Physiology Symposium . 2007.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on hippocampal injury in rats in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2: 14.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on the aortic artery in rats exposed to intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):88.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., The protective effect of melatonin on hippocampal injury of rats in intermittent hypoxia, FASEB Journal . 2007, 21(6): A824: 733.11.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor 1 activity in the rat lung and their responses to hypoxia, The Fourth International Huaxia Congress of Endocrinology. 2007.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia., Journal of Gerontology. 2007, 62A(1): 41-49.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expresssion and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia, Journal of Gerontology:Biological Sciences. 2007, 62A(1): 41-49.

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Expressions of hypoxia-inducible factor-1alpha, -2alpha, -3alpha in the rat carotid body during chronic and intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):89.

Lam S.S.Y., Tipoe G.L., Tjong Y.W., Liong E.C. and Fung M.L., Intermittent hypoxia regulates the renin-angiotensin system in the rat carotid body, 11^th Research Postgraduate Symposium HKU. 2006, 2:16.

Lam S.S.Y., Tipoe G.L., Liong E.C., Leung P.S. and Fung M.L., Up-regulation of a local renin-angiotensin system in the rat carotid body during chronic intermittent hypoxia, The Physiology Symposium (Hong Kong-Taiwan) Taipei. 2007.

Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H., Nanji A.A. and Tipoe G.L., Inhibition of inducible nitric oxide synthase (iNOS) or administration of L-arginine reverses the induction of hypoxia-inducible factor (HIF-1a) in experimental liver fibrosis, AALSD Meeting, San Francisco USA. 2006.

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcholic fatty liver disease (NAFLD) not requiring a high fat diet, Hepatology. 2006, 44(4) Suppl. 1: 181A.

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD) not requiring a high fat diet 1275 Suppl, Hepatology. 2006, 44(4): 181A.

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T. and Nanji A.A., Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4) Suppl. 1: 160A.

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorate pathological changes, oxidative stress and pro-inflammatory markrs in an animal model of non-alcoholic fatty liver disease [NAFLD], Hepatology. 2006, 44(4) Suppl. 1: 160A.

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.H.Y., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorated pathological changes, oxidative stress and pro-inflammatory markers in an animal model of non-alcoholic fatty liver disease (NAFLD) animal model 1063 Suppl 1, Hepatology . 2006, 44(4): 160A -1063.

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hamatological Disorders Drug Targets. 2007, 7(2): 135-144.

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 135-144.

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H. and Nanji A.A., Lau and A.A. Nanji. Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4): 160A, 1062.

Tjong Y.W., Jian K., Li M., Chen M., Gao T.M. and Fung M.L., Elevated endogenous NO increases Ca²⁺ flux via L-type Ca²⁺ channels by S-nitrosylation in rat hippocampal neurons during severe hypoxia and in-vitro ischemia, Free Radical Biology and Medicine. 2007, 42(1): 52-63.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Hippocampal nitric oxide deficit in intermittent hypoxia reduces large conductance calcium-activated potassium channel activity by nitrosylation in rat CA1 neurons., 4^th Congress of Federation of Asian-Oceanian Neuroscience Societies (FAONS) & 26^th Annual Meeting Hong Kong Society of Neuroscience, Hong Kong. 2006.

Tjong Y.W., Li M. and Fung M.L., Involvement of nitric oxide in reduced large conductance calcium-activated potassium channel activity in rat hippocampal CA1 neurons in intermittent hypoxia, Journal of Neurochemistry . 2006, (Suppl. 1): 66-67.

Tjong Y.W., Li M. and Fung M.L., Involvement of nitric oxide pathway in decreased large conductance calcium-activated potassium channel activity in hippocampal CA1 pyramidal neurons in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2.28.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Nitric oxide deficit by oxidative stress in intermittent hypoxia decreases large conductance calcium-activated potassium channel activity by nitrosylation in rat hippocampal CA1 neurons, The Second International Symposium on Healthy Aging, HKU, Hong Kong. 2007.

Yeung H.M., Kravtsov G.M., Ng K.M., Wong T.M. and Fung M.L., Chronic intermittent hypoxia alters Ca²⁺ handling in rat cardiomyocytes by augmented Na+/Ca²⁺exchange and ryanodine receptor activity in ischemia-reperfusion, American Journal of Physiology Cell Physiology. 2007, 292: C2046-2056.

Researcher : Ho HTB

List of Research Outputs

Ho H.T.B., Ko C.B., Cheung A.K.H., Lam A.K.M., Tam S., Chung S.K. and Chung S.S.M., Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice, Kidney International. 2007, 72: 63-71.

Researcher : Hung MW

List of Research Outputs

Fung M.L., Tjong Y.W., Hung M.W. and Li M., NO problem with sleep apnea? (Hong Kong-Taiwan) Taipei, The Physiology Symposium . 2007.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on hippocampal injury in rats in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2: 14.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on the aortic artery in rats exposed to intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):88.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., The protective effect of melatonin on hippocampal injury of rats in intermittent hypoxia, FASEB Journal . 2007, 21(6): A824: 733.11.

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hamatological Disorders Drug Targets. 2007, 7(2): 135-144.

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 135-144.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Hippocampal nitric oxide deficit in intermittent hypoxia reduces large conductance calcium-activated potassium channel activity by nitrosylation in rat CA1 neurons., 4^th Congress of Federation of Asian-Oceanian Neuroscience Societies (FAONS) & 26^th Annual Meeting Hong Kong Society of Neuroscience, Hong Kong. 2006.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Nitric oxide deficit by oxidative stress in intermittent hypoxia decreases large conductance calcium-activated potassium channel activity by nitrosylation in rat hippocampal CA1 neurons, The Second International Symposium on Healthy Aging, HKU, Hong Kong. 2007.

Researcher : Hwang ISS

List of Research Outputs

GO A.G.G., CHOW K.H.M., Hwang I.S.S. and Tang F., Adrenomedullin and its receptor components in adipose tissues: differences between white and brown fats and the effets of adrenergic stimulation., Peptides. 2007, 28: 920-927.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor 1 activity in the rat lung and their responses to hypoxia, The Fourth International Huaxia Congress of Endocrinology. 2007.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia., Journal of Gerontology. 2007, 62A(1): 41-49.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expresssion and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia, Journal of Gerontology:Biological Sciences. 2007, 62A(1): 41-49.

Li Y.Y., Hwang I.S.S., O W.S. and Tang F., Adrenomedullin peptide: gene expression of adrenomedullin, its receptors and receptor activiity modifying proteins, and receptor binding in rat testis-actions on testosterone secretion, Biology of Reproduction. 2006, 75: 183-188.

Man S.Y., Hwang I.S.S., Li Y.Y., O W.S., Sheng H.P. and Tang F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation, Neuropeptides. 2007, 41: 177-187.

Tang F., Hwang I.S.S., Wong P.F. and Li Y.Y., Adrenomedullin gene exprssion and peptide levels in the heart and blood vessels in streptozotocin-diabetic rats, Hormone and Metabolic Research. 2007, 398: 3-8.

Researcher : Kravtsov GM

List of Research Outputs

Yeung H.M., Kravtsov G.M., Ng K.M., Wong T.M. and Fung M.L., Chronic intermittent hypoxia alters Ca²⁺ handling in rat cardiomyocytes by augmented Na+/Ca²⁺exchange and ryanodine receptor activity in ischemia-reperfusion, American Journal of Physiology Cell Physiology. 2007, 292: C2046-2056.

Researcher : Kwok JCF

List of Research Outputs

Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4^th Congress of FAONS. 2006, 13.

Researcher : Lai CH

List of Research Outputs

Chan Y.S., Jiang Z.D. and Lai C.H., Pre- and postnatal development of the vestibular system. In: W.Q. Cai (Ed), Chapter 11. Science Publisher, Beijing; pp, Developmental Neurobiology. 2007, 391-403.

Chan Y.S., Lai C.H. and Shum D.K.Y., Spatial coding capacity of central otolith neurons. , Exp Brain Res. 2006, 173(2): 205-214.

Lai C.H., Tse Y.C., Shum D.K.Y. and Chan Y.S., Toward maturation of the vestibular system: neural circuits and neuronal properties, Neuroembryology and Aging. 2006, 3: 162-170.

Lee R.W.P., Lau J.W.K., Li C., Lai C.H. and Chan Y.S., Alteration in the distribution of otolith-related inferior olivary neurons after perinatal blockade of glutamate transmission in the vestibular nuclei, Proceedings of the 4th Congress of FAONS. 2006, 98.

Lee R.W.P., Tse Y.C., Sun J., Chan Y.S. and Lai C.H., Developmental expression of metabotropic glutamate receptor subtype R1a in rat vestibular nuclear neurons responding to linear accelerations., Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 9.

Li C., Liu J., Lai C.H. and Chan Y.S., Postnatal expression of glutamate receptor subunits in rat inferior olivary neurons responsive to horizontal linear acceleration, Neurosignals. 2006, 15: 125.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Change in the composition of perineuronal nets of central vestibular neurons following unilateral labyrinthectomy, Congress of FAONS. 2006, 100.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in Perineuronal Nets within the Rat Vestibular Nuclei during Postnatal Development and in Injury., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 12.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Society for Neuroscience (USA) Oct 14-18 Altanta, GA, USA. 2006, 550.12.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets of rat vestibular nuclear neurons after unilateral labyrinthectomy, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P41.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets within the rat vestibular nuclei during postnatal development, Proceedings of the 29th Annual Meeting of Japan Neuroscience Society, Kyoto Japan, July19-21. 2006, PS2A-F188.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Proceedings of the 4th Congress of FAONS, Nov. 30 - Dec. 2 Hong Kong. 2006, 100.

Sun X., Xia Q., Lai C.H., Shum D.K.Y., Chan Y.S. and He J., Corticofugal modulation on acoustically induced Fos expression in the rat auditory pathway, J. Comparative Neurology. 2007, 501: 509-525.

Tse Y.C., Zhou H., Lai C.H., Yung W.H. and Chan Y.S., Developmental profile of ionotropic glutamate receptors in the vestibular nucleus of rats: Analysis of miniature synaptic currents and c-fos expression, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 3.

Yiu C.N.S., Lai C.H. and Chan Y.S., Developmental expression of Fos protein in horizontal-canal related vestibular nuclear neurons of postnatal rat following angular acceleration, Neurosignals. 2006, 15: 132-133.

Yiu C.N.S., Chan Y.S. and Lai C.H., Developmental responsiveness of canal-related brainstem neurons to vertical head rotation, Proceedings of the 4^th Congress of FAONS. 2006, 102.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal motions, Proceedings of the 29^th Annual Meeting of Japan Neuroscience Society. 2006, PS2A-F187.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal rotational and translational motions, Neurosignals. 2006, 15: 142.

Researcher : Lai SK

List of Research Outputs

Chu J.Y.S., Lee L.T., Lai S.K., Chan Y.S., Yung W.H. and Chow B.K., The hypothalamo-neurohypophsial secretinergic pathway in regulating body water homeostasis, Proceedings of the 4th Congress of FAONS. 2006, 108-109.

Lai S.K., Yung W.H. and Chan Y.S., Synaptic regulation of glutamate receptor subunit composition in central vestibular neurons during neonatal development, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 13.

Tse Y.C., Lai S.K., Zhou H., Yung W.H. and Chan Y.S., AMPA and NMDA receptor properties in spinal vestibular neurons of developing rats, Neurosignals. 2006, 15: 143.

Researcher : Lam SSY

List of Research Outputs

Fung M.L., Lam S.S.Y., Wong T.P., Tjong Y.W. and Leung P.S., Carotid body AT₄ receptor expression and its upregulation in chronic hypoxia, The Open Cardiovascular Medicine Journal. 2007, 1: 1-7.

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Expressions of hypoxia-inducible factor-1alpha, -2alpha, -3alpha in the rat carotid body during chronic and intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):89.

Lam S.S.Y., Tipoe G.L., Tjong Y.W., Liong E.C. and Fung M.L., Intermittent hypoxia regulates the renin-angiotensin system in the rat carotid body, 11^th Research Postgraduate Symposium HKU. 2006, 2:16.

Lam S.S.Y., Tipoe G.L., Liong E.C., Leung P.S. and Fung M.L., Up-regulation of a local renin-angiotensin system in the rat carotid body during chronic intermittent hypoxia, The Physiology Symposium (Hong Kong-Taiwan) Taipei. 2007.

Researcher : Lau JWK

List of Research Outputs

Kwok J.C.F., Lau J.W.K., Ng K.Y., Shum D.K.Y. and Chan Y.S., Chondroitin sulfates enriched in the developing rat hindbrain restrict commissural projections of vestibular neurons, Neurosignals. 2006, 15: 123-123.

Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chau C.H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4th Congress of FAONS, Nov13-Dec2, Hong Kong. 2006, 13.

Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4^th Congress of FAONS. 2006, 13.

Lau J.W.K., Kwok J.C.F., Ng T.K., Chan Y.S. and Shum D.K.Y., Developing vestibular neurons display differential commissural projection patterns with digestion of chondroitin sulfates, Proceedings of the 4th Congress of FAONS Nov 30 - Dec 2, Hong Kong. 2006, 25.

Lee R.W.P., Lau J.W.K., Li C., Lai C.H. and Chan Y.S., Alteration in the distribution of otolith-related inferior olivary neurons after perinatal blockade of glutamate transmission in the vestibular nuclei, Proceedings of the 4th Congress of FAONS. 2006, 98.

Researcher : Le G

List of Research Outputs

Le G. and Ballard H.J., Adenosine-metabolising enzymes of skeletal muscle vascular endothelial cells., FASEB Journal. 2007, 21: 586.18.

Le G. and Ballard H.J., Isolation of skeletal muscle vascular endothelial cells. , Journal of the Hong Kong College of Cardiology . 2006, 14(2): 81.

Researcher : Lee HC

List of Research Outputs

Graeff R., Liu Q., Kriksunov I.A., Hao Q. and Lee H.C., Acidic residues at the active sites of CD38 and ADP-ribosyl cyclase determine NAADP synthesis and hydrolysis activities., Journal of Biological Chemistry. USA, The American Society for Biochemistry and Molecular Biology, 2006, 281: 28951-28957.

Lee H.C., Structure and enzymatic functions of human CD38, Molecular Medicine . 2006, 12: 317-323.

Liu Q., Kriksunov I.A., Graeff R., Hao Q. and Lee H.C., Structural basis for formation and hydrolysis of calcium messenger cyclic ADP-ribose by human CD38, Journal of Biological Chemistry. USA, The American Society for Biochemistry and Molecular Biology, 2007, 282: 5853-5861.

Liu Q., Kriksunov I.A., Graeff R., Munshi C., Lee H.C. and Hao Q., Structural basis for the mechanistic understanding human CD38 controlled multiple catalysis. , Journal of Biological Chemistry. USA, The American Society for Biochemistry and Molecular Biology, 2006, 281: 32861–32869.

Researcher : Lee RWP

List of Research Outputs

Lee R.W.P., Lau J.W.K., Li C., Lai C.H. and Chan Y.S., Alteration in the distribution of otolith-related inferior olivary neurons after perinatal blockade of glutamate transmission in the vestibular nuclei, Proceedings of the 4th Congress of FAONS. 2006, 98.

Lee R.W.P., Tse Y.C., Sun J., Chan Y.S. and Lai C.H., Developmental expression of metabotropic glutamate receptor subtype R1a in rat vestibular nuclear neurons responding to linear accelerations., Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 9.

Researcher : Li C

List of Research Outputs

Gao Y.P., Li C., Wang N.Q., Sun X., Chan Y.S. and He J.F., Cortically derived highly synchronized oscillation (0.3-3 Hz) in the auditory thalamus is via the direct excitatory pathway rather than the thalamic reticular nuclei, Proceedings of the 4^th Congress of FAONS. 2006, 115.

Guo Y.P., Sun X., Li C., Wang N.Q., Chan Y.S. and He J., c-fos expression in the auditory thalamus is triggered by corticofugal projections, Proceedings of National Academy of Sciences. 2007, 104: 11802-11807.

Lee R.W.P., Lau J.W.K., Li C., Lai C.H. and Chan Y.S., Alteration in the distribution of otolith-related inferior olivary neurons after perinatal blockade of glutamate transmission in the vestibular nuclei, Proceedings of the 4th Congress of FAONS. 2006, 98.

Li C., Guo Y.P., Chan Y.S. and He J., Postnatal development of corticofugal modulation in the auditory thalamus in rats, Soc. Neuroscience Abstract (U.S.A.) . 2006, 543: 1.

Li C., Liu J., Lai C.H. and Chan Y.S., Postnatal expression of glutamate receptor subunits in rat inferior olivary neurons responsive to horizontal linear acceleration, Neurosignals. 2006, 15: 125.

Researcher : Li GR

Project Title:	Volume-sensitive chloride current and cell volume regulation in human atrial myocytes
Investigator(s):	Li GR, Lau CP, Chiu SW, Tse HF
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2001

Abstract:

To determine the intracellular signaling pathways that regulate I_Cl.vol and cell volume in human atrium; to determine whether I_Cl.vol is persistently activated in atrial myocytes from patients with dilated atrial cardiomyopathy.

Project Title:	Ionic channels of mesenchymal stem cells from bone marrow and cell proliferation
Investigator(s):	Li GR, Lau CP, Chung SSM, Tse HF
Department:	Medicine
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	12/2003
Completion Date:	07/2006

Abstract:

To analyze the molecular identities of IK_DR, I_KCa, and I_Na in MSCs from rat bone marrow with semi-quantitative reverse transcript-polymeterase chain reaction (RT-PCR) and patch clamp techniques; to test the hypothesis that the three types of channels (IK_DR, I_KCa and I_Na) are involved in the proliferation of rat MSCs by determining cell proliferation in the absence and presence of channel blockers and modulators.

Project Title:	Studies on Ion Channels in Human Pre-adipocytes
Investigator(s):	Li GR, Lau CP
Department:	Medical Faculty
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2006

Abstract:

Ion channels play an important role in the physiological activities of many types of cells. In excitable cells, activation of ion channels generates action potentials and participates in excitation-contraction (muscles), excitation-secretion (glands), and impulse conduction (nerve and muscles), as well as repolarizing cell membrane potential. In proliferative cells, ion channels are found to be required for cell proliferation. Recent studies have demonstrated that several K channels, eg. inward rectifier K channels (IKir), delayed rectifier K channels (IKDR), ATP-sensitive K channel (IKATP), are involved in the cell cycling of lymphocytes, neuronal glial cells (e.g. astrocytes), epithelial cells, and cancer cells. Blockade of IKDR is believed to inhibit cell proliferation, whereas inhibition of IKIR promotes proliferation in rat spinal cord astrocytes. In addition, volume-sensitive chloride current (ICl.vol) is involved in the proliferation of several types of cells including vascular smooth muscle and endothelial cells, cancer cells etc. These studies indicate an important relationship between ion channels and cell proliferation. There has been a dramatic increase in the incidence of obesity resulting from an excess of white adipose tissue. Obesity is a prevalent health hazard in industrial countries, and is closely associated with the occurrence of type 2 diabetes and cardiovascular disease. Preadipocytes are the origin of fat cells of white adipose tissue. For the past two decades, in vitro systems have been extensively used to study adipocyte differentiation with preadipocytes. Although significant progress has been made in the dissection of the molecular and cellular events taking place during the transition from undifferentiated preadipocytes into mature round fat cells, control of adipocyte differentiation is not completely understood, especially ion channels and thire physiological roles in proliferation/differentiation have not been studied. The present proposal was to study ion channel expression and thire molecular identidies in human pre-adipocytes commercially obtained from CellSicence using whole-cell patch clamp and RT-PCR techniques, and to provide the experimental data for obtaining external RGC grant to further study whether/how ion channels are involved in proliferation/differentiation in human pre-adipocytes.

Project Title:	Studies on ion channels and cell proliferation in human cardiac fibroblasts
Investigator(s):	Li GR, Lau CP
Department:	Medical Faculty
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	01/2007

Abstract:

To analyze the molecular identities of I_KCa, IK_DR, I_CI.vol, and I_Na, in human cardiac fibroblasts with RT-PCR, Western blot analysis, and patch clamp technique; to test the hypothesis that these four types of channels (I_KCa, IK_DR, I_CI.vol, and I_Na are involved in the proliferation of human cardiac fibroblasts. Cell proliferation assays will be conducted in the absence and presence of channel blockers, short interfering RNA (siRNA) oligos targeted to IK_DR, I_KCa, I_CI.vol, and I_Na and channels, and/or signal modulators.

List of Research Outputs

Researcher : Li M

List of Research Outputs

Fung M.L., Tjong Y.W., Hung M.W. and Li M., NO problem with sleep apnea? (Hong Kong-Taiwan) Taipei, The Physiology Symposium . 2007.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Hippocampal nitric oxide deficit in intermittent hypoxia reduces large conductance calcium-activated potassium channel activity by nitrosylation in rat CA1 neurons., 4^th Congress of Federation of Asian-Oceanian Neuroscience Societies (FAONS) & 26^th Annual Meeting Hong Kong Society of Neuroscience, Hong Kong. 2006.

Tjong Y.W., Li M. and Fung M.L., Involvement of nitric oxide in reduced large conductance calcium-activated potassium channel activity in rat hippocampal CA1 neurons in intermittent hypoxia, Journal of Neurochemistry . 2006, (Suppl. 1): 66-67.

Tjong Y.W., Li M. and Fung M.L., Involvement of nitric oxide pathway in decreased large conductance calcium-activated potassium channel activity in hippocampal CA1 pyramidal neurons in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2.28.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Nitric oxide deficit by oxidative stress in intermittent hypoxia decreases large conductance calcium-activated potassium channel activity by nitrosylation in rat hippocampal CA1 neurons, The Second International Symposium on Healthy Aging, HKU, Hong Kong. 2007.

Researcher : Li YY

List of Research Outputs

Hwang I.S.S., Tang F., Leung P.L., Li Y.Y., Fan S.T. and Luk J.M.C., The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl(4)-induced rat liver cirrhosis, Regulatory Peptides. 2006, 135(1-2): 69-77.

Li Y.Y., Hwang I.S.S., O W.S. and Tang F., Adrenomedullin peptide: gene expression of adrenomedullin, its receptors and receptor activiity modifying proteins, and receptor binding in rat testis-actions on testosterone secretion, Biology of Reproduction. 2006, 75: 183-188.

Li Y.Y., O W.S. and Tang F., Ageing and adrenomedullin in the female reproductive system of the rat, Hong Kong Medical Journal. 2006, 12(6): 166 No. P204.

Man S.Y., Hwang I.S.S., Li Y.Y., O W.S., Sheng H.P. and Tang F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation, Neuropeptides. 2007, 41: 177-187.

O W.S., Li Y.Y. and Tang F., Adrenomedullin and its receptors in the testis, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No.P41: 52-53.

Tang F., Hwang I.S.S., Wong P.F. and Li Y.Y., Adrenomedullin gene exprssion and peptide levels in the heart and blood vessels in streptozotocin-diabetic rats, Hormone and Metabolic Research. 2007, 398: 3-8.

Tang F., Li Y.Y. and O W.S., Ageing and adrenomedullin in the male reproductive system of the rat, Hong Kong Medical Journal. 2006, 12(6): 165 No. P203.

Tang F., Li Y.Y. and O W.S., Ageing and adrenomedullin in the male reproductive system, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No. P39: 52.

Researcher : Liong EC

List of Research Outputs

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Expressions of hypoxia-inducible factor-1alpha, -2alpha, -3alpha in the rat carotid body during chronic and intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):89.

Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H., Nanji A.A. and Tipoe G.L., Inhibition of inducible nitric oxide synthase (iNOS) or administration of L-arginine reverses the induction of hypoxia-inducible factor (HIF-1a) in experimental liver fibrosis, AALSD Meeting, San Francisco USA. 2006.

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD) not requiring a high fat diet 1275 Suppl, Hepatology. 2006, 44(4): 181A.

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.H.Y., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorated pathological changes, oxidative stress and pro-inflammatory markers in an animal model of non-alcoholic fatty liver disease (NAFLD) animal model 1063 Suppl 1, Hepatology . 2006, 44(4): 160A -1063.

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H. and Nanji A.A., Lau and A.A. Nanji. Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4): 160A, 1062.

Researcher : Liu J

List of Research Outputs

Kwok J.C.F., Lau J.W.K., Liu J., Liu H., Chan Y.S. and Shum D.K.Y., Growth-inhibitory and facilitatory aspects of chondroitin sulfates in developing neural environments, Proceedings of the 4^th Congress of FAONS. 2006, 13.

Li C., Liu J., Lai C.H. and Chan Y.S., Postnatal expression of glutamate receptor subunits in rat inferior olivary neurons responsive to horizontal linear acceleration, Neurosignals. 2006, 15: 125.

Researcher : Lung MAKY

Project Title:	Endothelins in nasal mucosa: role in nasal congestion and decongestion
Investigator(s):	Lung MAKY
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To investigate the role of endothelins on the nasal mucosa, eliciting nasal congestion or decongestion, as well as the underlying vascular events and control mechanisms.

Project Title:	Muscarinic receptor subtypes in the control of nasal patency
Investigator(s):	Lung MAKY
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

Rhinitis, affecting about 20% of the world population and with increasing prevalence worlwide, is characterized by symptoms of mucosal hypereamia, engorgement, rhinorrea and nasal obstruction. In vivo studies in dogs show that acetylcholine induces nasal congestion at low doses (Lung & Wang, Ann Otol Rhinol Laryngol 1994; 103:646-651). Recent in vitro studies confirm that acetylcholine at low concentrations relaxes posterior collecting veins but contracts other collecting and outflow veins (Wang & Lung, Eur Resp J published online on May 31, 2006 as 10.1183/09031936.06.00077105). According to the vascular arrangements of the nasal mucosa, activation of muscarinic receptors in the posterior collecting veins will increase vascular capacitiance while activation of muscarinic receptors in the outflow veins will impair venous drainage. Both mechanisms acting together can easily promote nasal congestion especially when the number and reactivity of the mucarinic receptors are increased. An increase in the number of muscarinic receptors has been found in the nasal mucosa of human or animal models with nasal allergy (Naminatsu et al, Jpn J Pharmacol 1992; 59: 427-437). Radiolabelled ligand binding, autoradiography, competitive binding analysis and imumological studies suggest that M1, M2 and M3 receptor subtypes are present in the sinusoidal venous vessels of human inferior turbinate mucosa and among them M3 receptors are the most extensively distributed (Nakaya et al., Ann Otol Rhinol Laryngol 2002; 111: 593-597). However, the presence and distribution of muscarinci receptor subtypes in the collecting and outflow veins of the nasal mucosa are still unknown.The objective of this project is to to investigate the functional role of muscarinic receptors in the control of nasal patency. To achieve this, we will1. perform in vivo functional studies to characterize the muscarinic receptor subtypes present on the resistance and and capacitance vessels and to define their individual role in the control of nasal vascular and airway resistances.2. perform in vitro studies to characterize the muscarinic receptors present on the nasal collecting and outflow veins and to define their individual role in the control of airway resistance.3. perform immunohistochemical studies on the localization of muscarinic subtype receptors (M1, M2 and M3) as to confirm their presence and distribution in the nasal vasculature.

List of Research Outputs

Lung M.A.K.Y. and Wang M., Acetylcholine induces contractile and relaxant effects in canine nasal venous systems, European Respiratory Journal. United Kingdom, European Respiratory Society, 2006, 28: 839-846.

Researcher : Lung MKY

Project Title:	Endothelins in nasal mucosa: role in nasal congestion and decongestion
Investigator(s):	Lung MAKY
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To investigate the role of endothelins on the nasal mucosa, eliciting nasal congestion or decongestion, as well as the underlying vascular events and control mechanisms.

Project Title:	Muscarinic receptor subtypes in the control of nasal patency
Investigator(s):	Lung MAKY
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2006

Abstract:

List of Research Outputs

Researcher : Ma CW

List of Research Outputs

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Change in the composition of perineuronal nets of central vestibular neurons following unilateral labyrinthectomy, Congress of FAONS. 2006, 100.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in Perineuronal Nets within the Rat Vestibular Nuclei during Postnatal Development and in Injury., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 12.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Changes in perineuronal nets within the rat vestibular nuclei during postnatal development and in injury, Society for Neuroscience (USA) Oct 14-18 Altanta, GA, USA. 2006, 550.12.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets of rat vestibular nuclear neurons after unilateral labyrinthectomy, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P41.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Modifications in perineuronal nets within the rat vestibular nuclei during postnatal development, Proceedings of the 29th Annual Meeting of Japan Neuroscience Society, Kyoto Japan, July19-21. 2006, PS2A-F188.

Ma C.W., Lai C.H., Shum D.K.Y. and Chan Y.S., Proceedings of the 4th Congress of FAONS, Nov. 30 - Dec. 2 Hong Kong. 2006, 100.

Researcher : Man SY

List of Research Outputs

Man S.Y., Hwang I.S.S., Li Y.Y., O W.S., Sheng H.P. and Tang F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation, Neuropeptides. 2007, 41: 177-187.

Researcher : Mo HCW

List of Research Outputs

Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Melatonin inhibits the proliferation of hormone-refractory prostate cancer cells by up-regulating p27 Kip1 expression and down-regulating activated androgen signal transduction via membrane MT1 receptor activation., NCRI Cancer Conference, Birmingham, UK. 2006, B55.

Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention, Journal of Pineal Research. 2007, 42: 191-202.

Researcher : Ng KM

List of Research Outputs

Yeung H.M., Kravtsov G.M., Ng K.M., Wong T.M. and Fung M.L., Chronic intermittent hypoxia alters Ca²⁺ handling in rat cardiomyocytes by augmented Na+/Ca²⁺exchange and ryanodine receptor activity in ischemia-reperfusion, American Journal of Physiology Cell Physiology. 2007, 292: C2046-2056.

Researcher : Ng KY

List of Research Outputs

Kwok J.C.F., Lau J.W.K., Ng K.Y., Shum D.K.Y. and Chan Y.S., Chondroitin sulfates enriched in the developing rat hindbrain restrict commissural projections of vestibular neurons, Neurosignals. 2006, 15: 123-123.

Researcher : Poon AMS

Project Title:	Adrenomedullin in reproduction: gene expression of adrenomedullin in the female tract and the possible roles of adrenomedullin in the seminal plasma.
Investigator(s):	Poon AMS, O WS, Tang F
Department:	Physiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2007

Abstract:

BACKGROUND Our laboratories have shown that adrenomedullin (AM) is produced by the testis and the male sex accessory glands in the rat including the prostate, seminal vesicle and the epipidymis It inhibits steroidogenesis (Li et al. 2005) and inhibin secretion (Chan et al. unpublished results) and increases secretion in the epididymis (Hwang et al. 2003). AM levels are high in the seminal plasma (Marinoni et al. 2005) and one possible function of AM may be to increase motility (Yeung et al. personal communication). The actions of AM derived from the seminal plasma on the female tract have not been studied. One possible action is to increase cytokine production as vascular endothelial growth factor (VEGF), which is also present in the seminal plasma, has been shown to stimulate cytokine production in cultured human cervical cells (Robertson & Sharkey 2006) and AM is known to stimulate cytokine production in a variety of tissues The increase in cytokine production will in turn stimulate AM production from the uterine cells to form a positive feedback loop. The cytokines would then have inflammatory actions to supplement the anti-microbial actions of AM (Allaker et al. 2006). AM may also decrease the uterine contraction for implantation of the zygote. An inhibitory action of AM on uterine contraction has been reported (Yanagita et al. 2000). Another possible action of AM may be to decrease the production of reactive oxygen species (ROS) which may be important for the survival of the sperm and successful development of the fertilized ovum. It has been reported that the removal of the male sex accessory glands increases the vulnerability of the sperms to oxidative damage by ROS from leucocytes and dead sperms and from the uterine endometrium (O et al. 2006). AM has the ability to reduce the formation of ROS (Yoshimoto et al. 2004) and therefore AM in the seminal plasma may play an important anti-oxidative role in addition to the antioxidant enzymes known to be present in the seminal plasma. Our laboratories have also done some work to show that AM is produced in the ovary and the uterus. However, no work has been done on the rat oviduct. It has been reported that the presence of sperms may induce the production of AM from the mouse oviduct (Fazeli et al. 2004).The possible roles of AM secreted by the oviduct is unknown. It may increase oviductal secretion and/or decrease the motility of the oviduct, which may aid the fertilization of the ovum by the sperms. This possibility needs to be studied. Finally, the effects of AM on implantation and embryo development in early pregnancy have not been studied. Another important aspect is the possible role of AM in reducing immunity during pregnancy. The decrease in immunity during pregnancy is a well-known phenomenon and is important to prevent rejection of the foetus. The ability of AM to reduce immunosurveillance is an important factor for the development of tumours that are stimulated by AM (Zudaire et al. 2003). HYPOTHESIS Adrenomedullin in the seminal fluid may be important in reproduction by increasing the production of cytokines and by reducing the reactive oxygen species in the female tract. Adrenomedullin produced by the female tract may be important for fertilization and later for the maintenance of pregnancy. OBJECTIVES (1) To study the gene expression of AM and its receptor component proteins in the oviduct and the uterus. (Already done) (2) To study the effects of AM on cytokine production and the effect of cytokines on AM production in cultures of uterine fragments. (3) To study the effects of AM on ROS production in cultures of oviduct and uterus. (4) To study the effect of AM on oviductal secretion and motility. (5) To study the effect of AM on implantation and embryo development during early pregnancy. REFERENCES Allaker RP, Grosvenor PW, McAnerney DC, Sheehan BE, Srikanta BH, Pell K and Kapas S. (2006) Peptides 27, 661-666. Faseli A, Affara NA, Hubank M and Holt WV (2004) Biol. Reprod. 71, 60-65. Hwang ISS, Autelitano DJ, Wong PYD, Leung GPH and Tang F (2003) Biol. Reprod. 68, 2005-2012. Li YY, Hwang ISS, O WS and Tang F (2006) Biol. Reprod. 75, 183-188. Marinoni E, Di Iorio R, Villaccio B, Vellucci O, Di Netta T, Sessa M, Letizia C and Cosmi EV (2005) Eur. J. Obstet. Gynecol. Reprod. Biol. 122, 195-198. O WS, Chen H and Chow PH (2006) Mol. Cell. Endocrinol. 250, 80-83. Robertson S and Sharkey DJ (2006) Abstract O18, Society for Reproduction and Fertility Conference 2006, Leeds, UK. Yanagita T, Yamamoto R, Sugano T, Kobayashi H, Uezono Y, Yokoo H, Shiraishi S, Minami SI and Wada A (2000) Br. J. Pharmacol. 130, 1727-1730. Yoshimoto T, Fukai N, Sato R, Sugiyama T, Ozawa N, Schichire\i M and Hirata Y (2004) Endocrinology 145, 3331-3337. Zudaire E, Martiniez A and Cuttitta F (2003) Regul. Pept. 112, 175-183.

List of Research Outputs

Hughes M.R., Kitamura N., Bennett D.C., Gray D.A., Sharp P.J. and Poon A.M.S., Effect of melaotnin on salt gland and kidney function of gulls, Larus glaucescens, General and Comparative Endocrinology. Elsevier, 2007, 151: 300-307.

Hughes M.R., Bennett D.C., Gray D.A., Sharp P.J. and Poon A.M.S., Influences of sex and saline intake on diurnal changes in plasma melatonin and osmoregulatory hormones of Pekin ducks (Anas platyrhynchos), General and Comparative Endocrinology. Elsevier, 2006, 149: 205-214.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on hippocampal injury in rats in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2: 14.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on the aortic artery in rats exposed to intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):88.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., The protective effect of melatonin on hippocampal injury of rats in intermittent hypoxia, FASEB Journal . 2007, 21(6): A824: 733.11.

Mak A.S.Y., Wong W.H., Or C.K. and Poon A.M.S., Single surgeon's experience with Furlow palatoplasty and the fistula rate, Surgical Practice. 2006, 10: 138-142.

Mak S.Y., Wong W.H., Or C.K. and Poon A.M.S., Incidence and cluster occurrence of palatal fistula after Furlow palatoplasty by a single surgeon, Annals Plastic Surgery. Lippincott Williams & Wilkins, Ltd, 2006, 57: 55-59.

Poon A.M.S., Cheung K.M.C., Lu D. and Leong J.C.Y., Changes in melatonin receptors in relation to the development of scoliosis in pinealectomized chickens, Spine. Lippincott Williams & Wilkins, Inc, 2006, 31: 2043-2047.

Researcher : Sheng HP

List of Research Outputs

Man S.Y., Hwang I.S.S., Li Y.Y., O W.S., Sheng H.P. and Tang F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation, Neuropeptides. 2007, 41: 177-187.

Researcher : Shiu SYW

Project Title:	sPDZD2-induced protein profile changes in prostate cancer
Investigator(s):	Shiu SYW, Yao KM
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To express and purify sPDZD2 in E. coli, and to study the effects of the recombinant protein on the protein profiles of human prostate cancer to cells using a 'proteomics' approach.

Project Title:	Overexpression of sPDZD2 in prostate cancer cells
Investigator(s):	Shiu SYW, Yao KM
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2005

Abstract:

PDZ (PSD95, Discs-large, and ZO-1) domain containing protein 3 (PDZK3), also known as PDZ domain containing protein 2 (PDZD2), is a ubiquitously expressed protein of unknown function which has six PDZ domains. The protein is cleaved in a caspase-dependent mechanism to generate a secreted protein (sPDZD2), which may participate in extracellular signaling [Yeung et al. 2003, EMBO Rep 4: 412]. Interestingly, gene expression of PDZK3 has been reported to be upregulated in prostate cancer when compared with benign tissues Thus, it is believed that PDZK3, also named as activated in prostate cancer protein (AIPC), may play an important role in prostate tumorigenesis [Chaib et al. 2001, Cancer Res 61:2390]. Given that our ongoing studies have demonstrated that sPDZD2 protein is produced and secreted by human prostate cancer cell lines, we would like to postulate that sPDZD2 protein, a cleavage product of PDZD2, may play an important role in prostate cancer pathogenesis by modulating prostate cancer cell growth and differentiation. The objectives of this proposal are to 1) over-express sPDZD2 protein in prostate cancer cells, and 2) to study any effect of the protein on the expression of cell cycle and apoptosis-related proteins in the transfected cancer cells.

Project Title:	Structure-function studies of sPDZD2 protein and identification of its cellular targets
Investigator(s):	Shiu SYW, Yao KM
Department:	Physiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2007

Abstract:

Globally, prostate cancer has become the third most common cancer in men, with half a million new cases each year, amounting to about 10% of all male cancers. It is the most common cancer after skin cancer, and is the second leading cause of cancer-related death in men in the United States. The emergence of prostate cancer as a public health problem in developed countries has put tremendous pressure on the healthcare system to provide new and effective treatments. While there is significant research progress on understanding the signaling mechanisms of androgen, a key growth-promoting hormone, in prostate cancer initiation and progression, advanced prostate cancer patients still suffer from inevitable relapse of the disease after receiving the recommended treatment of androgen deprivation therapy (ADT). Clearly, there is an unmet clinical need to develop other novel therapeutic agents which can act effectively alone and/ or in combination with ADT to halt or reverse the progression of advanced prostate cancer. Such demand has fueled the search for novel endo-/para-/auto-crine growth-promoting and growth-inhibitory signaling pathways important in prostate cancer pathogenesis, which may yield new therapeutic agents or targets for anti-prostate cancer drug discovery. Recently, our group has identified the human sPDZD2 protein as a novel autocrine prostate tumor suppressor [Tam et al. Endocrinology 2006;147:5023-5033]. In this project we propose to construct a genetically-modified form of the endogenous human sPDZD2 protein with prostate cancer growth-inhibitory actions on both hormone-sensitive and hormone-insensitive prostate cancer cells. To further maximize the therapeutic potential of this endogenous sPDZD2 protein and to fuel the anti-prostate cancer drug development pipeline by the target-driven approach, efforts would be expended towards the molecular identification of the cellular targets, including the receptors, acted upon by the native and genetically-modified forms of human sPDZD2 protein.

List of Research Outputs

Cheng S.A., Tam C.W., Yao K.M. and Shiu S.Y.W., The anti-proliferative effects of sPDZD2 on prostate and non-prostate cancer cells, FASEB Journal. 9650 ROCKVILLE PIKE, BETHESDA,USA, FEDERATION AMER SOC EXP BIOL, 2007, 21 (5): A387.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on hippocampal injury in rats in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2: 14.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on the aortic artery in rats exposed to intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):88.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., The protective effect of melatonin on hippocampal injury of rats in intermittent hypoxia, FASEB Journal . 2007, 21(6): A824: 733.11.

Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human sPDZD2 protein, 3rd PacRim Breast and Prostate Cancer Meeting, Kingfisher Bay Resort, Fraser Island, Queensland, Australia. 2006, 41.

Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor, Endocrinology. 2006, 147: 5023-5033.

Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Melatonin inhibits the proliferation of hormone-refractory prostate cancer cells by up-regulating p27 Kip1 expression and down-regulating activated androgen signal transduction via membrane MT1 receptor activation., NCRI Cancer Conference, Birmingham, UK. 2006, B55.

Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention, Journal of Pineal Research. 2007, 42: 191-202.

Researcher : Sun X

List of Research Outputs

Gao Y.P., Li C., Wang N.Q., Sun X., Chan Y.S. and He J.F., Cortically derived highly synchronized oscillation (0.3-3 Hz) in the auditory thalamus is via the direct excitatory pathway rather than the thalamic reticular nuclei, Proceedings of the 4^th Congress of FAONS. 2006, 115.

Guo Y.P., Sun X., Li C., Wang N.Q., Chan Y.S. and He J., c-fos expression in the auditory thalamus is triggered by corticofugal projections, Proceedings of National Academy of Sciences. 2007, 104: 11802-11807.

Sun X., Xia Q., Lai C.H., Shum D.K.Y., Chan Y.S. and He J., Corticofugal modulation on acoustically induced Fos expression in the rat auditory pathway, J. Comparative Neurology. 2007, 501: 509-525.

Sun X., Chan Y.S. and He J., Expression of Fos protein in the medial geniculate body of cochlear-ablated and cortical-activated rats, Neurosignals. 2006, 15: 128-129.

Researcher : Tam CW

List of Research Outputs

Cheng S.A., Tam C.W., Yao K.M. and Shiu S.Y.W., The anti-proliferative effects of sPDZD2 on prostate and non-prostate cancer cells, FASEB Journal. 9650 ROCKVILLE PIKE, BETHESDA,USA, FEDERATION AMER SOC EXP BIOL, 2007, 21 (5): A387.

Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human sPDZD2 protein, 3rd PacRim Breast and Prostate Cancer Meeting, Kingfisher Bay Resort, Fraser Island, Queensland, Australia. 2006, 41.

Tam C.W., Cheng S.A., Ma R.Y.M., Yao K.M. and Shiu S.Y.W., Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor, Endocrinology. 2006, 147: 5023-5033.

Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Melatonin inhibits the proliferation of hormone-refractory prostate cancer cells by up-regulating p27 Kip1 expression and down-regulating activated androgen signal transduction via membrane MT1 receptor activation., NCRI Cancer Conference, Birmingham, UK. 2006, B55.

Tam C.W., Mo H.C.W., Yao K.M. and Shiu S.Y.W., Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention, Journal of Pineal Research. 2007, 42: 191-202.

Researcher : Tam KW

List of Research Outputs

Tam K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Chondroitinases ABC I and II from Proteus Vulgaris for Therapuetic Use: Cloning and Characterization., 11th Research Postgraduate Symposium, 7 Dec. 2006. The University of Hong Kong, Li Ka Shing Faculty of Medicine. 2006.

Tam K.W., Li R.A., Chan Y.S. and Shum D.K.Y., Recombinant expression and characterization of chondroitinse ABC I and II, The 2nd Int'l Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4 Hong Kong. 2007, P8.

Researcher : Tang F

Project Title:	Adrenomedullin in the rat testis: paracrine actions and its interaction with endothelin
Investigator(s):	Tang F, O WS
Department:	Physiology
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2004

Abstract:

To study the gene expression and levels of adrenomedullin and also its receptors and binding in the whole testis and in the Leydig cells and Sertoli cells, and the types of receptor activity modifying proteins expressed in these cells which will determine whether these cells respond to adrenomedullin or CGRP or both; to investigate the effects of adrenomedullin on steoidogenesis in the Leydig cells, contraction of seminferous tubules and Sertoli cell secretion in the presence or absense of CGRP or endothelin, gonadotrophins and testosterone.

Project Title:	Adrenomedullin as a new metabolic hormone: its distribution and actions in the liver, muscles and adipose tissues, and possible roles in metabolic syndrome and in ageing.
Investigator(s):	Tang F
Department:	Physiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2006

Abstract:

Overall objective. To study the effects of adrenomedullin (AM) on glucose and fat metabolism in the liver, muscle and fat and its roles in metabolic syndrome. Specific objectives. (1) To study the effects of AM on glucose uptake in the liver, muscles and fat, gluconeogenesis in the liver, lipogenesis and lipolysis in fat, and free fatty acid oxidation in the fat and muscle strips. (2) To study the effects of AM on plasma glucose and FFA levels in vivo. (3) To determine the changes of AM levels and gene expression in animal models of metabolic syndrome: (a) the Zucker rat with deficiency of leptin receptors, and (b) rats fed with a high fat diet. (4) To study the parameters listed in (3) in ageing rats if time and resource permit. Ageing is one specific type of metabolic syndrome in the rat because all old rats are obese as a result of the lack of exercise due to confinement to a small space. Background & Rationale. Adrenomedullin (AM) is a newly discovered peptide hormone, which is widely distributed and have many functions, mostly paracrine. AM and its receptors have been reported in the liver and white adipose tissues and this has been confirmed by us. Our laboratory is the first (and the only one so far) to confirm the presence of AM and its gene expression in the skeletal muscles. The metabolic actions of adrenomedullin is largely unknown. Two other members of the calcitonin family (to which AM belongs) i.e. amylin and CGRP, are known to decrease glucose uptake (Abatty & Cooper 2004) and to increase insulin resistance (Molina et al. 1990). AM, like amylin, is produced by the pancreatic islets and inhibits insulin secretion (Martinez et al. 2006). Our preliminary data suggest that AM may increase insulin-mediated glucose uptake by the rat liver cells and by a mouse adipocyte cell line (3T3L1). Another group (Shimosawa et al. 2005) has reported a possible effect of AM on glucose transport in the soleus msucle of a transgenic mouse. The effects of AM on fat metabolism is controversial. AM may increase lipogenesis (Fukai et al. 2005) but is known to inhibit (Hamancey et al. 2005) or stimualte (Linshield et al. 2005) lipolysis in vitro. We hypothesize that AM may be another adipokine like leptin and adiponectin to decrease insulin resistance but is different from these two in acting mainly locally (paracrine action). It may do so in a number of ways, including increase in glucose uptake, decrease in gluconeogenesis and increase in free fatty acid oxidation. If this hypothessis is correct, one would expect changes in AM level and gene expression in the liver, fat and muscles in metabolic syndrome, such as in the Zucker rats or in obesity induced by a high fed diet. Morevover, there is an increase of oxidative stress in metabolic syndrome (Shimosawa & Fujita 2005) and AM is an important anti-oxidant. Metabolic syndrome is characterized by increases in insulin resistance, obesity, hypertension and oxidative stress (Morley 2004). Hypothesis. The hypothesis is that AM may have important actions in the metabolism of the liver, muscle and adipose tissues to modulate insulin resistance, and hence may play important roles in the development of metabolic syndrome . Reference. 1. Abatty T & Cooper GJ (2004) Peptides 25: 2119-2125. 2. Molina JM, Cooper GJ, Leighton B et al. (1990) Diabetes 39: 260-265. 3. Martinez A, Weaver C, Lopez J et al. (1996) Endocrinology 137: 2626-2632. 4. Shimosawa T & Fujita T (2005) Drug News Perspect. 18: 185-189. 5. Fukai N, Yoshimoto T, Sugiyama T et al. (2005) Amer. J. Physiol. 288: E56-62. 6. Hamacey R, Senard JM, Pathak A et al. (2005) FASEB J. 19: 1045-1047. 7. Linshield P, Saboek D, Zulewski H et al. (2005) Endocrinolgoy 46: 2699-2708. 8. Morley LE (2004) J. Gerontol. 59A: 139-142.

Project Title:	Ageing and drenomedullin in the female reproductive system
Investigator(s):	Tang F, O WS
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	10/2006

Abstract:

Objectives: (1) To study the age-related changes in adrenomedullin (AM) and the gene expresion of preproAM, its receptor (CRLR, calcitonin receptor-like receptor) and RAMPS (receptor activity modifying proteins) in the ovary, oviduct and testis. (2) To determine the chgnes in AM receptor binding with age in the ovary, oviduct and the uterus by Scatchard plot analysis. (3) To correlate the above with the age-related changes in plasma AM, and serum oestadiol and progesterone levels. Background: In our laboratory, adrenomedullin (AM) , and the gene expression of AM and its receptor components (i.e. CRLR, calcitonin receptor-like receptor, and RAMPs, receptor activity modifying proteins) are found in the ovary, oviduct and utersus of the rat (supportd by an earlier grant by CRCG). In the male, ageing is associated with an increase in the above parmeters in the testis, but a decrease in the sex accessory glands including the seminal vesicles and the ventral prostate (Tang et al. 2006). These changes are believed to be the cause or the result of a decrease in testosterone production by the testis. The changes of AM gene expression in the uterus is related to the oestrogen level (Cameron et al. 2002 ). AM is believed to lay some roles in the female including the development of the corpus luteum (Abe et al. 2000), steroidogenesis (Moriyama et al. 2000), uterine blood flow (Makino et al. 1999), uterine contraction (Upton et al. 1997), implantation (Zhang et al.2005), and the development of the placenta (Penchalani et al. 2004). It is well-established that plasma oestrogen levels decrease with age, particularly after menopause. Hypothesis: We hypothesize that there are age-related changes in AM and its receptor component proteins that may be related to the change in oestrogen levels. As AM is known to increase steroidogenesis, we might expect to find a decrease in ovarian AM with ageing. Similarly, since AM in the uterus is increased by oestorogen, the age-related decrease in plasma oestrogen level would result in a decline in AM in the uterus. These changes in the AM system would impair the proper functioning of the ovary and uterine receptivity. Abe K, Minegishi T, Ibuki Y et al. (2000) Fetil Steril. 74: 141-5 Cameron VA, Auteltintano DJ, Evans JJ et al. (2002) Am. J. Physiol. 282: E139-146. Makino et al. (1999) Eur. J. Pharmacol. 385: 129. Moriyama T, Otani T, Maruo T. Eur. J. Endocrinol. 142: 671-6. Penchalini J, Wimalawansa SJ, Yallampalli C. (2004) Biol. Reprod. 71: 1475-83. Tang F, Li YY and O WS (2006) Abstrtact, Conference of the Society for Reproduction and Fertility. Upton PD, Austin C, Taylor GM et al. (1997) Endocrinology 138: 2506-14. Zhang X, Green KE, Yallampalli C et al. (2005) Biol. Reprod. 73: 619-626.

List of Research Outputs

Chan Y.F., O W.S. and Tang F., Testicular adrenomedullin and endothelin interaction, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No.P40.

GO A.G.G., CHOW K.H.M., Hwang I.S.S. and Tang F., Adrenomedullin and its receptor components in adipose tissues: differences between white and brown fats and the effets of adrenergic stimulation., Peptides. 2007, 28: 920-927.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor 1 activity in the rat lung and their responses to hypoxia, The Fourth International Huaxia Congress of Endocrinology. 2007.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia., Journal of Gerontology. 2007, 62A(1): 41-49.

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expresssion and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia, Journal of Gerontology:Biological Sciences. 2007, 62A(1): 41-49.

Hwang I.S.S., Tang F., Leung P.L., Li Y.Y., Fan S.T. and Luk J.M.C., The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl(4)-induced rat liver cirrhosis, Regulatory Peptides. 2006, 135(1-2): 69-77.

Li Y.Y., Hwang I.S.S., O W.S. and Tang F., Adrenomedullin peptide: gene expression of adrenomedullin, its receptors and receptor activiity modifying proteins, and receptor binding in rat testis-actions on testosterone secretion, Biology of Reproduction. 2006, 75: 183-188.

Li Y.Y., O W.S. and Tang F., Ageing and adrenomedullin in the female reproductive system of the rat, Hong Kong Medical Journal. 2006, 12(6): 166 No. P204.

Man S.Y., Hwang I.S.S., Li Y.Y., O W.S., Sheng H.P. and Tang F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation, Neuropeptides. 2007, 41: 177-187.

O W.S., Li Y.Y. and Tang F., Adrenomedullin and its receptors in the testis, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No.P41: 52-53.

Tang F., Hwang I.S.S., Wong P.F. and Li Y.Y., Adrenomedullin gene exprssion and peptide levels in the heart and blood vessels in streptozotocin-diabetic rats, Hormone and Metabolic Research. 2007, 398: 3-8.

Tang F., Li Y.Y. and O W.S., Ageing and adrenomedullin in the male reproductive system of the rat, Hong Kong Medical Journal. 2006, 12(6): 165 No. P203.

Tang F., Li Y.Y. and O W.S., Ageing and adrenomedullin in the male reproductive system, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No. P39: 52.

Researcher : Tjong YW

List of Research Outputs

Fung M.L., Lam S.S.Y., Wong T.P., Tjong Y.W. and Leung P.S., Carotid body AT₄ receptor expression and its upregulation in chronic hypoxia, The Open Cardiovascular Medicine Journal. 2007, 1: 1-7.

Fung M.L., Tjong Y.W., Hung M.W. and Li M., NO problem with sleep apnea? (Hong Kong-Taiwan) Taipei, The Physiology Symposium . 2007.

Lam S.S.Y., Tipoe G.L., Tjong Y.W., Liong E.C. and Fung M.L., Intermittent hypoxia regulates the renin-angiotensin system in the rat carotid body, 11^th Research Postgraduate Symposium HKU. 2006, 2:16.

Tjong Y.W., Jian K., Li M., Chen M., Gao T.M. and Fung M.L., Elevated endogenous NO increases Ca²⁺ flux via L-type Ca²⁺ channels by S-nitrosylation in rat hippocampal neurons during severe hypoxia and in-vitro ischemia, Free Radical Biology and Medicine. 2007, 42(1): 52-63.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Hippocampal nitric oxide deficit in intermittent hypoxia reduces large conductance calcium-activated potassium channel activity by nitrosylation in rat CA1 neurons., 4^th Congress of Federation of Asian-Oceanian Neuroscience Societies (FAONS) & 26^th Annual Meeting Hong Kong Society of Neuroscience, Hong Kong. 2006.

Tjong Y.W., Li M. and Fung M.L., Involvement of nitric oxide in reduced large conductance calcium-activated potassium channel activity in rat hippocampal CA1 neurons in intermittent hypoxia, Journal of Neurochemistry . 2006, (Suppl. 1): 66-67.

Tjong Y.W., Li M. and Fung M.L., Involvement of nitric oxide pathway in decreased large conductance calcium-activated potassium channel activity in hippocampal CA1 pyramidal neurons in intermittent hypoxia, 11^th Research Postgraduate Symposium HKU. 2006, 2.28.

Tjong Y.W., Li M., Hung M.W. and Fung M.L., Nitric oxide deficit by oxidative stress in intermittent hypoxia decreases large conductance calcium-activated potassium channel activity by nitrosylation in rat hippocampal CA1 neurons, The Second International Symposium on Healthy Aging, HKU, Hong Kong. 2007.

Researcher : Tse YC

List of Research Outputs

Lai C.H., Tse Y.C., Shum D.K.Y. and Chan Y.S., Toward maturation of the vestibular system: neural circuits and neuronal properties, Neuroembryology and Aging. 2006, 3: 162-170.

Lee R.W.P., Tse Y.C., Sun J., Chan Y.S. and Lai C.H., Developmental expression of metabotropic glutamate receptor subtype R1a in rat vestibular nuclear neurons responding to linear accelerations., Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 9.

Tse Y.C., Lai S.K., Zhou H., Yung W.H. and Chan Y.S., AMPA and NMDA receptor properties in spinal vestibular neurons of developing rats, Neurosignals. 2006, 15: 143.

Tse Y.C., Zhou H., Lai C.H., Yung W.H. and Chan Y.S., Developmental profile of ionotropic glutamate receptors in the vestibular nucleus of rats: Analysis of miniature synaptic currents and c-fos expression, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 3.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal motions, Proceedings of the 29^th Annual Meeting of Japan Neuroscience Society. 2006, PS2A-F187.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal rotational and translational motions, Neurosignals. 2006, 15: 142.

Researcher : Tu J

List of Research Outputs

Tu J. and Ballard H.J., Increase in interstitial ATP of rat Extensor digitorum longus muscle during lactic acid infusion. , Journal of the Hong Kong College of Cardiology . 2006, 14(2): 74.

Tu J. and Ballard H.J., Increase in interstitial ATP of rat soleus muscle during lactic acid infusion., FASEB Journal. 2007, 21: 586.17.

Researcher : Wong PF

List of Research Outputs

Tang F., Hwang I.S.S., Wong P.F. and Li Y.Y., Adrenomedullin gene exprssion and peptide levels in the heart and blood vessels in streptozotocin-diabetic rats, Hormone and Metabolic Research. 2007, 398: 3-8.

Researcher : Wong TM

Project Title:	Signaling mechanism of preconditioning with U50, 488H in the rat - the role of K_atp channels
Investigator(s):	Wong TM
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To determine the roles of two types of K_ATP channels, mitochondrial and sarcolemmal in delayed cardioprotection of preconditioning with a [kappa] opioid receptor [kappa]-OR agonist, U50, 488H; to determine the relationship between K_ATP channels and heat shock protein 70 (HSP70), which has already been shown to mediate delayed cardioprotection of preconditioning with U50, 488H.

Project Title:	Effects of testosterone on intracellular Ca² transient and its response to adrenoceptor stimulation
Investigator(s):	Wong TM
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To understand the role of T on the regulation of cardiac functions; to understand the interaction between T and ARs.

Project Title:	Cardioprotective effect of oestrogen–Ca2+ homeostasis and the signalling mechanisms
Investigator(s):	Wong TM
Department:	Physiology
Source(s) of Funding:	Small Project Funding
Start Date:	01/2006

Abstract:

Eostrogen (E), the predominant female sex hormone, is well known to protect the heart against ischaemic insults. We showed in our previous studies that E confers cardioprotection by suppressing the beta1-adrenoceptor (b1-AR). We also found in preliminary studies that the cardioprotection resulting from interaction (cross-talk) between E and 1-AR is accompanied by attenuation of intracellular Ca overload, indicating that the cross-talk may restore the impaired Ca homeostasis. The first objective of the proposed study is to determine the effects of E on Ca handling at different sites of the ventricular myocyte. Since Ca homeostasis is regulated in aprt by two signalling pathways, namely Gs-protein/adenylyl cyclase/cAMP/protein kinase A and Ca2+/calmodulin kinase II (CaMKII), we also propose to determine whether and how estrogen affects Ca homeostasis via thse two pathways. With the support from the University and the Research Grants Council, the PI has been working on role of estrogen in cardiac function and cardioprotection in the past few years. The proposed study is a contimuation of the existing research. So the PI has all the expertise for the proposed study in terms of facility and knowledge in the field of study.

List of Research Outputs

Chen J., Tong Y. and Wong T.M., Diosgenin against myocardial injury induced by ischemia and reperfusion in rats, 　Fifth CGCM. zhuhai, 2006.

Chen J. and Wong T.M., Protective effects of Diosgenin against myocardial injury induced by ischemia and reperfusion , In: Bao KX, 　2006 international symposium for traditional Chinese medicine and integration of traditionalchinese & western medicine. seattle, 2006.

Fung M.L. and Wong T.M., Metabolic syndrome in an Asian population and agents and targets for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 77-78.

Li Y., Yu C.K., Wong G.T.C., Irwin M.G. and Wong T.M., Remifentanil confers Delayed Cardioprotection in Vivo, The Institute of Cardiovascular Science and Medicine. LKS Faculty of Medicine, The University of Hong Kong 10th Anniversary Scientific Meeting 2006.

Yeung H.M., Kravtsov G.M., Ng K.M., Wong T.M. and Fung M.L., Chronic intermittent hypoxia alters Ca²⁺ handling in rat cardiomyocytes by augmented Na+/Ca²⁺exchange and ryanodine receptor activity in ischemia-reperfusion, American Journal of Physiology Cell Physiology. 2007, 292: C2046-2056.

Researcher : Yeung HM

List of Research Outputs

Yeung H.M., Kravtsov G.M., Ng K.M., Wong T.M. and Fung M.L., Chronic intermittent hypoxia alters Ca²⁺ handling in rat cardiomyocytes by augmented Na+/Ca²⁺exchange and ryanodine receptor activity in ischemia-reperfusion, American Journal of Physiology Cell Physiology. 2007, 292: C2046-2056.

Researcher : Yiu CNS

List of Research Outputs

Yiu C.N.S., Lai C.H. and Chan Y.S., Developmental expression of Fos protein in horizontal-canal related vestibular nuclear neurons of postnatal rat following angular acceleration, Neurosignals. 2006, 15: 132-133.

Yiu C.N.S., Chan Y.S. and Lai C.H., Developmental responsiveness of canal-related brainstem neurons to vertical head rotation, Proceedings of the 4^th Congress of FAONS. 2006, 102.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal motions, Proceedings of the 29^th Annual Meeting of Japan Neuroscience Society. 2006, PS2A-F187.

Yiu C.N.S., Tse Y.C., Lai C.H. and Chan Y.S., Developmental responsiveness of vestibular-related brainstem neurons to horizontal rotational and translational motions, Neurosignals. 2006, 15: 142.

Researcher : Zhou H

List of Research Outputs

Tse Y.C., Lai S.K., Zhou H., Yung W.H. and Chan Y.S., AMPA and NMDA receptor properties in spinal vestibular neurons of developing rats, Neurosignals. 2006, 15: 143.

Tse Y.C., Zhou H., Lai C.H., Yung W.H. and Chan Y.S., Developmental profile of ionotropic glutamate receptors in the vestibular nucleus of rats: Analysis of miniature synaptic currents and c-fos expression, Soc. Neuroscience Abstract (U.S.A.). 2006, 550: 3.

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