Prof Tsim has chosen the vertebrate neuromuscular junctions as the
model system to study the cellular and molecular events that lead to
the formation of synapses during development and regeneration. The
post-synaptic specializations, induced by motor neuron, include the
expression and aggregation of acetylcholine receptors (AChRs),
acetylcholinesterase (AChE) and other synaptic molecules in the
muscle cell. Results from our laboratory have indicated that
adenosine 5'-triphosphate (ATP), co-released with acetylcholine from
the motor neurons, induces the expression of AChR/AChE by activating
its receptors, P2Y subtype. Prof Tsim intends to use molecular
genetic methods to : (i) determine the role of ATP and P2Y receptors
in directing the formation of post-synaptic specializations; (ii)
reveal the signaling pathway of P2Y receptor-mediated AChR/AChE gene
activation in muscle; (iii) map the transcriptional elements of the
catalytic subunit and the collagen-tail (ColQ) subunit of AChE
during muscle development. In addition, Prof Tsim has developed
molecular technique to determine the genetic and chemical properties
of traditional Chinese medicine (TCM).
Biochemistry and neurobiology (from 2005):
1. Li,
W., Pi, R., Chan, H.H., Fu, H., Lee, N.T., Tsang, H.W., Pu, Y., Chang, D.C., Li,
C., Luo, J., Xiong, K., Li, Z., Xue, H., Carlier, P.R., Pang, Y., Tsim,
K.W.K., Li, M. and Han, Y. (2005): Novel dimeric acetylcholinesterase
inhibitor bis7-tacrine, but not donepezil, prevents glutamate-induced neuronal
apoptosis by blocking N-methyl-D-aspartate receptors. J Biol Chem. 280:
18179-18188.
2. Ling,
K.K., Siow, N.L., Choi, R.C. and Tsim, K.W.K. (2005): ATP
potentiates the formation of AChR aggregate in the co-culture of NG108-15 cells
with C2C12 myotubes. FEBS Lett. 579: 2469-2474.
3. Ting,
A.K., Siow, N.L., Kong, L.W. and
Tsim, K.W.K.
(2005): Transcriptional regulation of acetylcholinesterase-associated collagen
ColQ in fast- and slow-twitch muscle fibers. Chem Biol Interact. 157-158:
63-70.
4. Siow,
N.L., Xie, H.Q., Choi, R.C. and Tsim, K.W.K. (2005): ATP induces
the post-synaptic gene expression in neuron-neuron synapses: Transcriptional
regulation of AChE catalytic subunit. Chem Biol Interact. 157-158: 423-6.
5. Xie,
H.Q., Siow, N.L., Peng, H.B., Massouli赌,
J. and Tsim, K.W.K. (2005): Regulation of PRiMA: membrane anchor
of acetylcholinesterase (AChE) in neuron and muscle. Chem Biol Interact.
157-158: 432.
6. Li,
W., Lee, N.T., Fu, H., Kan, K.K., Pang, Y., Li, M., Tsim, K.W.K.,
Li, X. and Han, Y. (2006): Neuroprotection via inhibition of nitric oxide
synthase by bis(7)-tacrine. Neuroreport. 17: 471-474.
7. Ji,
Z.N., Dong, T.T., Ye, W.C., Choi, R.C., Lo, C.K. and Tsim, K.W.K.
(2006): Ginsenoside Re attenuate beta-amyloid and serum-free induced
neurotoxicity in PC12 cells. J Ethnopharmacol. 107: 48-52.
8. Fu,
H., Li, W., Lao, Y., Luo, J., Lee, N.T., Kan, K.K., Tsang, H.W., Tsim
K.W.K., Pang, Y., Li, Z., Chang, D.C., Li, M. and Han, Y. (2006):
Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating
L-type calcium channels. J Neurochem. 98: 1400-1410.
9. Wan,
D.C., Zhang, X., Siow, N.L., Xie, H.Q. and Tsim, K.W.K. (2006):
Chick acetylcholinesterase promoter regulation. J Mol Neurosci. 30:
33-34.
10.
Tsim,
K.W.K.,
Xie, H.Q., Ting, A.K., Siow, N.L., Ling, K.K. and Kong, L.W.
(2006): Transcriptional control
of different acetylcholinesterase subunits in formation and maintenance of
vertebrate neuromuscular junctions. J Mol Neurosci. 30: 189-192.
11.
Zhu, H., Gao, W., Jiang, H., Jin, Q.H., Shi, Y.F.,
Tsim, K.W.K. and Zhang, X.J. (2007): Regulation of
acetylcholinesterase expression by calcium signaling during calcium ionophore
A23187- and thapsigargin-induced apoptosis. Int J Biochem Cell Biol. 39:
93-108.
12.
Li, W., Xue, J., Niu, C., Fu, H., Lam, C.S., Luo,
J., Chan, H.H., Xue, H., Kan, K.K., Lee, N.T., Li, C., Pang, Y., Li, M.,
Tsim, K.W.K., Jiang, H., Chen, K., Li, X. and Han, Y. (2007):
Synergistic neuroprotection by bis(7)-tacrine via concurrent blockade of
N-methyl-D-aspartate receptors and neuronal nitric-oxide synthase. Mol
Pharmacol. 71: 1258-1267.
13.
Zhu, J.T., Choi, R.C., Chu, G.K., Cheung, A.W., Gao,
Q.T., Li, J., Jiang, Z.Y., Dong, T.T. and Tsim, K.W.K. (2007):
Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12
cells: a comparison of different flavonoids in activating estrogenic effect and
in preventing beta-amyloid-induced cell death. J Agric Food Chem. 55:
2438-2445.
14.
Xie, H.Q., Choi, R.C., Leung, K.W., Siow, N.L.,
Kong, L.W., Lau, F.T., Peng, H.B. and Tsim, K.W.K. (2007):
Regulation of a transcript encoding the proline-rich membrane anchor of globular
muscle acetylcholinesterase. The suppressive roles of myogenesis and innervating
nerves. J Biol Chem. 282: 11765-11775.
15.
Choi, R.C., Ting, A.K., Lau, F.T., Xie, H.Q.,
Leung, K.W., Chen, V.P., Siow, N.L and Tsim, K.W.K. (2007):
Calcitonin gene-related peptide induces the expression of acetylcholinesterase-associated
collagen ColQ in muscle: a distinction in driving two different promoters
between fast- and slow-twitch muscle fibers. J Neurochem. 102: 1316-1328.
16.
Fu, H., Li, W., Liu, Y., Lao, Y., Liu, W., Chen,
C., Yu, H., Lee, N.T., Chang, D.C., Li, P., Pang, Y., Tsim, K.W.K.,
Li, M. and Han, Y. (2007): Mitochondrial proteomic analysis and characterization
of the intracellular mechanisms of bis(7)-tacrine in protecting against
glutamate-induced excitotoxicity in primary cultured neurons. J Proteome Res.
6: 2435-2446.
17.
Fu, H., Li, W., Luo, J., Lee, N.T., Li, M.,
Tsim, K.W.K., Pang, Y., Youdim, M.B. and Han, Y. (2008): Promising
anti-Alzheimer's dimer bis(7)-tacrine reduces beta-amyloid generation by
directly inhibiting BACE-1 activity. Biochem Biophys Res Commun. 366:
631-636.
18.
Choi, R.C., Simon, J., Tsim, K.W.K.
and Barnard, E.A. (2008): Constitutive and agonist-induced dimerizations of the
P2Y1 receptor: relationship to internalization and scaffolding. J Biol Chem.
283: 11050-11063.
19.
Tsim,
K.W.K.,
Choi, R.C., Xie, H.Q., Zhu, J.T., Leung, K.W., Lau, F.T., Chu, G.K., Chen, V.P.,
Mok, M.K., Cheung, A.W. and Bi, C.W. (2008). Transcriptional control of
different subunits of AChE in muscles: signals triggered by the motor
nerve-derived factors. Chem Biol Interact. 175: 58-63.
20.
Choi, R.C., Mok, M.K., Cheung, A.W., Siow, N.L.,
Xie, H.Q. and Tsim, K.W.K. (2008).
Regulation of PRiMA-linked
G(4) AChE by a cAMP-dependent signaling pathway in cultured rat pheochromocyoma
PC12 cells. Chem Biol Interact. 175: 76-78.
21.
Xie, H.Q., Leung, K.W., Chen, V.P., Lau, F.T., Liu,
L.S., Choi, R.C. and Tsim, K.W.K. (2008).
The promoter activity of
proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase in
muscle: suppressive roles of myogenesis and innervating nerve.
Chem Biol Interact. 175: 79-82.
22.
Lau, F.T., Choi, R.C., Xie, H.Q., Leung, K.W.,
Chen, V.P., Zhu, J.T., Bi, C.W., Chu, G.K. and Tsim, K.W.K.
(2008).
Myocyte enhancer factor 2
mediates acetylcholine-induced expression of acetylcholinesterase- associated
collagen ColQ in cultured myotubes. Mol Cell Neurosci. 39:
429-438.
23.
Ng, Y.P., Wu, Z., Wise, H., Tsim, K.W.K.,
Wong, Y.H. and Ip, N.Y. (2009).
Differential and
Synergistic effect of nerve growth factor and cAMP on the regulation of early
response genes during neuronal differentiation. Neurosignals.
17: 111-120.
24.
Xie, H.Q.,
Choi, R.C., Leung, K.W., Chen, V.P., Chu, G.K. and Tsim, K.W.K.
(2009) Transcriptional regulation of proline-rich membrane anchor (PRiMA) of
globular form acetylcholinesterase in neuron: an inductive effect of neuron
differentiation. Brain Res.
(Published online)
Traditional Chinese medicine (from 2005):
1. Tsim,
K.W.K.
(2005): Danggui Buxue Tang (DBT, Chinese Angelica Decoction): a sample
trial in TCM standardization. Asia-Pacific Biotech News (APBN). 8:
1316-1321.
2. Zhao,
K.J., Dong, T.T.X., Lo, CK., Tu, P.F. and Tsim, K.W.K. (2005):
Species identification of Dyers woad leaf by DNA sequences of 5S-rRNA spacer
domain and random amplified polymorphic DNA (RAPD). Oriental Pharmacy and
Experimental Medicine. 5: 117-123.
3. Cheung,
J.K.H., Li, S.P. and Tsim, K.W.K. (2005): Authentication and
quality control of Cordyceps sinensis, a traditional Chinese medicine
known as winter-worm summer-grass. Oriental Pharmacy and Experimental
Medicine. 5: 262-271.
4. Yang,
F.Q., Li, S.P., Chen, Y., Lao, S.C., Wang, Y.T., Dong, T.T.X. and Tsim,
K.W.K. (2005): Identification and quantitation of eleven sesquiterpenes
in three species of Curcuma rhizomes by pressurized liquid extraction and gas
chromatography-mass spectrometry. J Pharm Biomed Anal. 39: 552-558.
5. Carles,
M., Cheung, M.K., Moganti, S., Dong, T.T.X., Tsim, K.W.K., Ip,
N.Y. and Sucher, N.J. (2005): A DNA microarray for the authentication of toxic
traditional Chinese medicinal plants. Planta Med. 71: 580-584.
6. Xia,
Q., Zhao, K.J., Huang, Z.G., Zhang, P., Dong, T.T.X., Li, S.P. and Tsim,
K.W.K. (2005): Molecular genetic and chemical assessment of Rhizoma
Curcumae in China. J Agric Food Chem. 53: 6019-6026.
7. Dong,
T.T.X., Zhao, K.J., Huang, W.Z., Leung, K.W. and Tsim, K.W.K.
(2005): Orthogonal array design in optimizing the extraction efficiency of
active constituents from roots of Panax notoginseng. Phytother Res. 19:
684-688.
8. Wu,
X.M., Gao, X.M., Tsim, K.W.K. and Tu, P.F. (2005): An
arabinogalactan isolated from the stems of Cistanche deserticola induces the
proliferation of cultured lymphocytes. Int J Biol Macromol. 37: 278-282.
9. Kung,
S.D. and Tsim, K.W.K. (2006):
Modernization of Traditional Chinese Medicine-A Prospect From Western Medicine (從西方思維看中藥現代化).
Joint Publishing (HK) Co. Ltd.
10.
Li, S.P., Yang, F.Q. and Tsim, K.W.K.
(2006): Quality control of Cordyceps sinensis, a valued traditional Chinese
medicine. J Pharm Biomed Anal. 41: 1571-1584.
11.
Dong, T.T.X., Zhao, K.J., Gao, Q.T., Ji, Z.N., Zhu,
T.T., Li, J., Duan, R., Cheung, A.W. and Tsim, K.W.K. (2006):
Chemical and biological assessment of a chinese herbal decoction containing
Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in
having optimized properties. J Agric Food Chem. 54: 2767-2774.
12.
Mak, D.H., Chiu, P.Y., Dong, T.T.X., Tsim,
K.W.K. and Ko, K.M. (2006): Dang-Gui Buxue Tang produces a more potent
cardioprotective effect than its component herb extracts and enhances
glutathione status in rat heart mitochondria and erythrocytes. Phytother Res.
20: 561-567.
13. Li,
S.P., Zhang, G.H., Zeng, Q., Huang, Z.G., Wang, Y.T., Dong, T.T.X. and
Tsim, K.W.K. (2006): Hypoglycemic activity of polysaccharide, with
antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine.
13: 428-433.
14.
Gao, Q.T., Cheung, J.K., Li, J., Chu, G.K., Duan,
R., Cheung, A.W., Zhao, K.J., Dong, T.T.X. and Tsim, K.W.K.
(2006): A Chinese herbal decoction, Danggui Buxue Tang, prepared from Radix
Astragali and Radix Angelicae Sinensis stimulates the immune responses.
Planta Med. 72: 1227-31.
15.
Wu, X., Dai, H., Huang, L., Gao, X., Tsim,
K.W.K., and Tu, P. (2006): A fructan, from Radix ophiopogonis,
stimulates the proliferation of cultured lymphocytes: structural and functional
analyses. J Nat Prod. 69: 1257-1260.
16.
Ji, Z.N., Zhao, W.Y., Liao, G.R., Choi, R.C., Lo,
C.K., Dong, T.T.X. and Tsim, K.W.K. (2006): In vitro estrogenic
activity of formononetin by two bioassay systems. Gynecol Endocrinol. 22:
578-584.
17.
Wan, J.B., Li, P., Li, S., Wang, Y., Dong, T.T.X.
and Tsim, K.W.K. (2007): Simultaneous determination of 11 saponins
in Panax notoginseng using HPLC-ELSD and pressurized liquid extraction. J Sep
Sci. 29: 2190-2196.
18.
Gao, Q.T., Choi, R.C., Cheung, A.W., Zhu, J.T., Li,
J., Chu, G.K., Duan, R., Cheung, J.K., Jiang, Z.Y., Dong, X.B., Zhao, K.J.,
Dong, T.T.X. and Tsim, K.W.K. (2007): Danggui buxue tang – a
Chinese herbal decoction activates the phosphorylations of extracellular
signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells.
FEBS Lett. 581: 233-240.
19.
Chiu, P.Y., Leung, H.Y., Siu, A.H., Poon, M.K.,
Dong, T.T.X., Tsim, K.W.K. and Ko, K.M. (2007): Dang-Gui Buxue
Tang protects against oxidant injury by enhancing cellular glutathione in H9c2
cells: role of glutathione synthesis and regeneration. Planta Med. 73:
134-141.
20.
Li, J., Dong, X., Jiang, Y., Gao, Q., Jiang, Z.,
Cheung, A.W., Duan, R., Dong, T.T.X., Tu, P. and Tsim, K.W.K.
(2007): Simultaneous determination of phenols in Radix Polygalae by high
performance liquid chromatography: quality assurance of herbs from different
regions and seasons. J Sep Sci. 30: 2583-2589.
21.
Ng, K.L., Lam, C.C., Fu, Z., Han, Y.F., Tsim,
K.W.K. and Wong, W.K. (2007): Cloning and characterization of the yjeA
gene, encoding a novel deoxyribonuclease, from Bacillus subtilis. J Biochem.
142: 647-654.
22.
Gao, Q.T., Cheung, J.K., Li, J., Jiang, Z.Y., Chu,
G.K., Duan, R., Cheung, A.W., Zhao, K.J., Choi, R.C., Dong, T.T.X. and
Tsim, K.W.K. (2007): A Chinese herbal decoction, Danggui Buxue Tang,
activates extracellular signal-regulated kinase in cultured T-lymphocytes.
FEBS Lett. 581: 5087-93.
23.
Dong, X.B., Li, J., Jiang, Y., Zheng, Y., Dong,
T.T.X., Tu, P.F. and Tsim, K.W.K. (2007): Determination of
tenuifolin in tianwang buxinwan and guipiwan by HPLC. Zhongguo Zhong Yao Za
Zhi. 32: 1647-1649.
24.
Gao, Q., Li, J., Cheung, J.K., Duan, J., Ding, A.,
Cheung, A.W., Zhao, K., Li, W.Z, Dong, T.T.X. and Tsim, K.W.K.
(2007): Verification of the formulation and efficacy of Danggui Buxue Tang (a
decoction of Radix Astragali and Radix Angelicae Sinensis): an exemplifying
systematic approach to revealing the complexity of Chinese herbal medicine
formulae. Chin Med. 2: 12.
25.
Gao, Q.T., Cheung, J.K., Choi, R.C., Cheung, A.W.,
Li, J., Jiang, Z.Y., Duan, R., Zhao, K.J., Ding, A.W., Dong, T.T.X. and
Tsim, K.W.K. (2008): A Chinese herbal decoction prepared from Radix
Astragali and Radix Angelicae Sinensis induces the expression of erythropoietin
in cultured Hep3B cells. Planta Med. 74: 392-395.
26. Li,
J., Li, W.Z., Huang, W., Cheung, A.W., Bi, C.W., Duan, R., Guo, A.J., Dong,
T.T.X. and Tsim, K.W.K. (2009)
Quality evaluation of
Rhizoma Belamcandae (Belamcanda chinensis (L.) DC.) by using high-performance
liquid chromatography coupled with diode array detector and mass spectrometry.
J Chromatogr A. 1216: 2071-2078.
27. Choi,
R.C., Gao, Q.T., Cheung, A.W., Zhu, J.T., Lau, F.T., Li, J., Li, W.Z., Chu, G.K.,
Duan, R., Cheung, J.K., Ding, A.W., Zhao, K.J., Dong, T.T.X. and Tsim,
K.W.K. (2009)
A Chinese herbal
decoction, Danggui Buxue Tang, stimulates proliferation, differentiation and
gene expression of cultured osteosarcoma cells: genomic approach to reveal
specific gene activation. Evid Based Complement Alternat Med.
(Published online)
28. Li,
W.Z., Li, J., Bi, C.W., Cheung, A.W., Huang, W., Duan, R., Choi, R.C., Chen, I.S.,
Zhao, K.J., Dong, T.T.X., Duan, J.A. and Tsim, K.W.K. (2009)
Can Rhizoma Chuanxiong
replace Radix Angelica Sinensis in the traditional Chinese herbal decoction
Danggui Buxue Tang? Planta Med. (Published online)
29. Guo,
A.J., Choi, R.C., Cheung, A.W., Li, J., Chen, I.X., Dong, T.T., Tsim,
K.W.K., Lau, B.W. (2009) Stimulation of Apolipoprotein A-IV expression
in Caco-2/TC7 enterocytes and reduction of triglyceride formation in 3T3-L1
adipocytes by potential anti-obesity Chinese herbal medicines. Chin Med.
(Published
online)
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