Seizure-induced changes in mitochondrial redox status

Seizure-induced changes in mitochondrial redox status
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DOI:
10.1016/j.freeradbiomed.2005.08.026
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发表时间:
2006-01-15
影响因子:
7.4
通讯作者:
Patel, M
Patel, M
中科院分区:
医学1区
文献类型:
--
作者:
Liang, LP;Patel, M

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本研究的目的是通过测量海马组织和线粒体中的谷胱甘肽(GSH)和谷胱甘肽二硫醚(GSSG)水平来确定癫痫诱导的氧化应激。kainate诱导的大鼠癫痫持续状态(SE)导致海马组织和线粒体中GSH/GSSG比值的时间依赖性降低。然而,与海马组织相比,线粒体部分GSH/GSSG比率的变化更为显著。这分别伴随着海马体组织和谷胱甘肽过氧化物酶活性的轻度增加和谷胱甘肽还原酶活性的降低。由于辅酶A (CoASH)及其与谷胱甘肽的二硫化物(CoASSG)主要在线粒体内区隔,因此在组织中测量它们是为了克服亚细胞分离后测量谷胱甘肽/谷胱甘肽的相关问题。海马组织CoASH/CoASSG比值在盐酸盐诱导SE后下降,其变化的时间和幅度与线粒体GSH/GSSG水平平行。半胱氨酸,谷胱甘肽的限速前体,在海碱盐给药后海马组织和线粒体分数降低。综上所述,氧化还原状态的改变为癫痫引起的线粒体氧化应激提供了进一步的证据。(c) 2005爱思唯尔公司版权所有。
The aim of this study was to determine seizure-induced oxidative stress by measuring hippocampal glutathione (GSH) and glutathione disulfide (GSSG) levels in tissue and mitochondria. Kainate-induced status epilepticus (SE) in rats resulted in a time-dependent decrease of GSH/GSSG ratios in both hippocampal tissue and mitochondria. However, changes in GSH/GSSG ratios were more dramatic in the mitochondrial fractions compared to hippocampal tissue. This was accompanied by a mild increase in glutathione peroxidase activity and a decrease in glutathione reductase activity in hippocampal tissue and mitochondria, respectively. Since coenzyme A (CoASH) and its disulfide with GSH (CoASSG) are primarily compartmentalized within mitochondria, their measurement in tissue was undertaken to overcome problems associated with GSH/GSSG measurement following subcellular fractionation. Hippocampal tissue CoASH/CoASSG ratios were decreased following kainate-induced SE, the time course and magnitude of change paralleling mitochondrial GSH/GSSG levels. Cysteine, a rate-limiting precursor of glutathione was decreased following kainate administration in both hippocampal tissue and mitochondrial fractions. Together these changes in altered redox status provide further evidence for seizure-induced mitochondrial oxidative stress. (c) 2005 Elsevier Inc. All rights reserved.