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

被引：56
作者：
Lu, Yan [1 ,2 ]
Zhang, Jing [1 ,2 ]
Ma, Bingqing [1 ]
Li, Kexue [1 ,2 ]
Li, Xiaoyu [1 ]
Bai, Hui [2 ]
Yang, Qing [2 ]
Zhu, Xudong [1 ,2 ]
Ben, Jingjing [1 ,2 ]
Chen, Qi [1 ,2 ]
机构：
[1] Nanjing Med Univ, Lab Mol Intervent Cardiovasc Dis, Atherosclerosis Res Ctr, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China
来源：
NEUROCHEMISTRY INTERNATIONAL | 2012年 / 61卷 / 05期
基金：
中国国家自然科学基金;
关键词：
Glycine; Cerebral ischemia/reperfusion; Apoptosis; SH-SY5Y cell; siRNA; Neurons; Glycine receptor; ARTERY OCCLUSION; ISCHEMIA-REPERFUSION; PROTECTION; RECEPTOR; MODEL; CYTOPROTECTION; STROKE; KINASE; CELLS; DEATH;
D O I：
10.1016/j.neuint.2012.07.005
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 alpha 1 (GlyR alpha 1) 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. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码：649 / 658
页数：10
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