Glycine attenuates cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis in mice

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• 作者：Yan Lu ; Jing Zhang ; Bingqing Ma ; Kexue Li ; Xiaoyu Li ; Hui Bai ; Qing Yang ; Xudong Zhu ; Jingjing Ben ; Qi Chen
• 关键词：CNS ; central nervous system ; ERK1/2 ; extracellular signal-regulated kinase 1 and 2 ; GlyRs ; glycine receptors ; GlyR ¦Á1 ; glycine receptor ¦Á1 ; IACUC ; institutional animal care and use committee ; I/R ; ischemia/reperfusion ; JNK ; c-Jun N-terminal kinase ; LDH
• 刊名：Neurochemistry International
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：61
• 期：5
• 页码：649-658
• 全文大小：1170 K

文摘

Glycine is a cytoprotector to protect cells against ischemic damage by counteracting neuronal depolarization. However, whether it can directly inhibit neuronal apoptosis is unknown. In this study, we demonstrated that glycine could attenuate ischemia/reperfusion (I/R) induced cerebral infarction and improved neurological outcomes in mice. The protective effect of glycine was associated with reduction of terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) positive cells, deactivation of phosphor-JNK, inhibition of caspase-3 cleavage, down-regulation of FasL/Fas, and up-regulation of bcl-2 and bcl-2/bax in the mouse I/R penumbra. The beneficial effect of glycine against oxygen and glucose deprivation (OGD) induced injury was also confirmed in SH-SY5Y cells as well as in primary cultured neurons, which was significantly dampened by knockdown of glycine receptor ¦Á1 (GlyR ¦Á1) with siRNA transfection or by preventing glycine binding with glycine receptor using a specific antibody against glycine receptor. These results suggest that glycine antagonize cerebral I/R induced injury by inhibiting apoptosis in mice. Glycine could block both extrinsic and intrinsic apoptotic pathways for which GlyR may be required.