Mechanism of neuroprotective function of taurine.
Taurine has potent protective function against glutamate-induced neuronal injury presumably through its function in regulation of intracellular free calcium level, [Ca2+]i. In this communication, we report that taurine exerts its protective function through one or more of the following mechanisms: 1. Inhibition of glutamate-induced calcium influx through L-, N- and P/Q-type voltage-gated calcium channels and NMDA receptor calcium channel; 2. Attenuation of glutamate-induced membrane depolarization; 3. Prevention of glutamate-induced apoptosis via preventing glutamate-mediated down-regulation of Bcl-2; 4. Prevention of cleavage of Bcl-2 by calpain. This action of taurine is due to its inhibition on glutamate induced calpain activation. Based on these observations, we propose that taurine protects neurons against glutamate-induced neurotoxicity in part, by preventing glutamate-induced membrane depolarization, elevation of [Ca2+]i, activation of calpain, reduction of Bcl-2 and apoptosis.
Wu
Jang-Yen
JY
Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA. jwu@fau.edu
Wu
Heng
H
Jin
Ying
Y
Wei
Jianning
J
Sha
Di
D
Prentice
Howard
H
Lee
Hsin-Hsueh
HH
Lin
Chun-Hua
CH
Lee
Yi-Hsuan
YH
Yang
Ling-Ling
LL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000494:pharmacology; D015640:Ion Channel Gating; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; D013654:Taurine; D018698:Glutamic Acid; C033668:calpastatin; D002154:Calpain