Glycine attenuates cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis in mice
Glycine attenuates cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis in mice
复制标题
甘氨酸通过抑制小鼠神经元凋亡减轻脑缺血/再灌注损伤
DOI：
10.1016/j.neuint.2012.07.005
复制
发表时间：
2012-10-01
影响因子：
4.2
通讯作者：
Chen, Qi
中科院分区：
文献类型：
--
作者：
Lu, Yan;Zhang, Jing;Chen, Qi
甘氨酸是一种细胞保护剂，通过对抗神经元去极化来保护细胞免受缺血性损伤。但其是否能直接抑制神经细胞凋亡尚不清楚。在这项研究中，我们证明甘氨酸可以减轻缺血/再灌注（I/R）引起的脑梗死并改善小鼠的神经系统结果。甘氨酸的保护作用与小鼠 I/R 半暗带中末端脱氧核苷酸转移酶生物素-dUTP 缺口末端标记 (TUNEL) 阳性细胞的减少、磷-JNK 的失活、 caspase-3 裂解的抑制、FasL/Fas 的下调以及 bcl-2 和 bcl-2/bax 的上调有关。甘氨酸对缺氧和葡萄糖剥夺 (OGD) 诱导的损伤的有益作用也在 SH-SY5Y 细胞以及原代培养的神经元中得到证实，通过 siRNA 转染敲低甘氨酸受体 α 1 (GlyR α 1) 或使用针对甘氨酸受体的特异性抗体阻止甘氨酸与甘氨酸受体结合，可显着抑制这种损伤。这些结果表明甘氨酸通过抑制小鼠细胞凋亡来对抗脑缺血再灌注引起的损伤。甘氨酸可以阻断可能需要 GlyR 的外源性和内源性细胞凋亡途径。 (C) 2012 Elsevier Ltd. 保留所有权利。
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.