Protective function of taurine in glutamate‐induced apoptosis in cultured neurons

Abstract

Previously, we showed that taurine protects neurons against glutamate-induced excitotoxicity by inhibiting the glutamate-induced increase of [Ca2+](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 [Ca2+](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.

Excitotoxicity effects of glutamate on human neuroblastoma SH-SY5Y cells via oxidative damage

“…One is associated with an exaggerated and prolonged rise in intracellular Ca 2+ concentration following the over-stimulation of NMDA receptors [21,22] . Another involves the oxidative injury pathway which is independent of NMDA receptors [11] and can be specifically inhibited by vitamin E, the caspase inhibitor, extracellular cystine in an elevated level, and the removal of extracellular glutamate [23,24] .…”

Taurine Exerts Robust Protection Against Hypoxia and Oxygen/Glucose Deprivation in Human Neuroblastoma Cell Culture

“…In the ischemic hypothalamic nucleus of mice, taurine also attenuated the expression of caspase-8 and caspase-9 (Taranukhin et al 2008 ;Leon et al 2009 ) .…”

Biochemical and Pathophysiological Aspects of the Treatment of Hepatic Encephalopathy in Rats

“…[53] [55] In addition, we have also demonstrated that glutamate-induced activation of calpain is inhibited by taurine resulting in decrease of formation of hetero-dimers of Bcl-2 and Bax and the subsequent release of cytochrome C and the apoptosis cascade. [56] The effect of taurine on brain astrocytes might be involved in the mechanism by which this amino acid prevents brain edema in in vivo conditions. Cauli et al (2014) [57] mentioned that the predominant role of neuroinflammation rather than brain edema in the pathogenesis of CNS injury in HE.…”