Premium
Protective function of taurine in glutamate‐induced apoptosis in cultured neurons
Author(s) -
Leon Rebecca,
Wu Heng,
Jin Ying,
Wei Jianning,
Buddhala Chandana,
Prentice Howard,
Wu JangYen
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21926
Subject(s) - taurine , glutamate receptor , cytochrome c , apoptosis , excitotoxicity , calpain , microbiology and biotechnology , programmed cell death , biology , chemistry , biochemistry , amino acid , enzyme , receptor
Previously, we showed that taurine protects neurons against glutamate‐induced excitotoxicity by inhibiting the glutamate‐induced increase of [Ca 2+ ] i . In this study, we report that taurine prevents glutamate‐induced chromosomal condensation, indicating that taurine inhibits glutamate‐induced apoptosis. We found that Bcl‐2 was down‐regulated while Bax was up‐regulated by glutamate treatment, and these changes were prevented in the presence of taurine. We have also shown that taurine inhibits glutamate‐induced activation of calpain. Furthermore, calpastatin, a specific calpain inhibitor, also prevented glutamate‐induced cell death. Here we propose the mechanisms underlying glutamate‐induced apoptosis and taurine's inhibition of glutamate‐induced apoptosis to be as follows: glutamate stimulation induces [Ca 2+ ] i elevation, which in turn activates calpain; activation of calpain leads to a reduction of Bcl‐2:Bax ratios; with decreased Bcl‐2:Bax ratios Bax homodimers form, Bax homodimerization, and translocation to the mitochondria result in the release of cytochrome c ; released cytochrome c in turn activates a downstream caspase cascade leading to apoptosis. The antiapoptotic function of taurine is due to its inhibition of glutamate‐induced membrane depolarization. © 2008 Wiley‐Liss, Inc.