Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischemia
Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischemia
复制标题
DOI：
10.1016/s0197-0186(03)00133-5
复制
发表时间：
2004-02-01
影响因子：
4.2
通讯作者：
Sims, NR
中科院分区：
文献类型：
--
作者：
Anderson, MF;Nilsson, M;Sims, NR
谷氨酸是细胞抗氧化防御的核心成分。我们最近报道了一个早期和选择性的损失总（还原加氧化）谷胱甘肽从线粒体分离大鼠大脑中动脉闭塞后。这种线粒体谷胱甘肽耗竭与随后再灌注过程中发生的组织损伤有明显的相关性，这表明它可能是细胞丢失易感性的重要决定因素。在本研究中，我们研究了谷胱甘肽乙酯在体内治疗是否可以调节线粒体谷胱甘肽在大脑中，这种治疗是否可以影响局灶性缺血的反应。大脑中动脉闭塞导致线粒体谷胱甘肽的持续依赖性部分丧失，这进一步支持了我们先前的研究结果。在诱导单侧局灶性缺血之前立即双侧注射谷胱甘肽乙酯导致动脉闭塞后2小时非缺血半球（生理盐水处理对照组的190%）和缺血半球（对照组的240%）纹状体线粒体中谷胱甘肽的大幅增加。此时，总组织谷胱甘肽不受酯处理的影响。在酯处理后的非缺血性纹状体中，在闭塞3小时观察到线粒体谷胱甘肽的较小增加，但在这个时间点，谷胱甘肽在缺血半球的线粒体中没有显著改变。缺血前用谷胱甘肽酯治疗并没有显著改变缺血2或3小时后48小时评估的组织梗死体积。这些研究表明，谷胱甘肽乙酯是一个非常有效的调节剂的线粒体谷胱甘肽池在完整的大脑，并提供了一个有用的手段，进一步研究这种抗氧化剂的作用，在缺血和其他脑疾病的组织损伤的发展。(C)2003 Elsevier Ltd.保留所有权利。
Glutathione is a central component in the antioxidant defences of cells. We have recently reported an early and selective loss of total (reduced plus oxidised) glutathione from mitochondria isolated from rat brain following occlusion of the middle cerebral artery. This mitochondrial glutathione depletion showed an apparent association with the tissue damage that developed during subsequent reperfusion, suggesting that it could be an important determinant of susceptibility to cell loss. In the present study, we have investigated whether in vivo treatment with glutathione ethyl ester can modulate mitochondrial glutathione in the brain and whether this treatment can influence the response to focal ischemia. In further support of our previous findings, middle cerebral artery occlusion caused a duration-dependent partial loss of mitochondrial glutathione. Bilateral injections of glutathione ethyl ester immediately prior to induction of unilateral focal ischemia resulted in a substantial increase in glutathione in mitochondria from the striatum of both the non-ischemic hemisphere (190% of saline-treated controls) and the ischemic hemisphere (240% of controls) at 2 h after arterial occlusion. Total tissue glutathione was not affected by the ester treatment at this time. A smaller increase in mitochondrial glutathione was observed at 3 h of occlusion in the non-ischemic striatum following ester treatment but at this time point glutathione was not significantly altered in mitochondria from the ischemic hemisphere. Pre-ischemic treatment with glutathione ester did not significantly change the volume of tissue infarction assessed at 48 h following ischemia for 2 or 3 h. These studies demonstrate that glutathione ethyl ester is a highly effective modulator of the mitochondrial glutathione pool in the intact brain and provides a useful means for further investigating the role of this antioxidant in the development of tissue damage in ischemia and other brain disorders. (C) 2003 Elsevier Ltd. All rights reserved.