Mitochondrial superoxide production in kainate-induced hippocampal damage
Mitochondrial superoxide production in kainate-induced hippocampal damage
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DOI：
10.1016/s0306-4522(00)00397-3
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发表时间：
2000-01-01
期刊：
影响因子：
3.3
通讯作者：
Patel, M
中科院分区：
文献类型：
--
作者：
Liang, LP;Ho, YS;Patel, M
本研究的目的是确定线粒体超氧阴离子自由基介导的氧化损伤在癫痫诱导的神经元死亡中的作用。使用乌头酸酶失活作为超氧化物产生的指标，我们发现，在神经元死亡之前，系统地给大鼠红藻氨酸可以增加海马体中线粒体超氧化物的产生。8-羟基-2-脱氧鸟苷，一种DNA的氧化损伤，在给予红藻氨酸后，在大鼠的海马区也增加。四(4-苯甲酸)卟啉锰(III)是一种催化抗氧化剂，它能抑制红藻氨酸诱导的大鼠海马区线粒体超氧化物生成、8-羟基-2-脱氧鸟苷的形成和神经元的丢失。过量表达线粒体超氧化物歧化酶-2的转基因小鼠可减轻红藻氨酸诱导的线粒体超氧化物歧化产物的增加和海马神经元的丢失。我们认为这些结果表明线粒体超氧化物歧化酶的产生在红藻氨酸惊厥所致的海马神经元病理中发挥了作用。(C)2000年IBRO。爱思唯尔科学有限公司出版。版权所有。
The objective of this study was to determine the role of mitochondrial superoxide radical-mediated oxidative damage in seizure-induced neuronal death. Using aconitase inactivation as an index of superoxide production, we found that systemic administration of kainate in rats increased mitochondrial superoxide production in the hippocampus at times preceding neuronal death. 8-Hydroxy-2-deoxyguanosine, an oxidative lesion of DNA, was also increased in the rat hippocampus following kainate administration. Manganese(III) tetrakis(4-benzoic acid)porphyrin, a catalytic antioxidant, inhibited kainate-induced mitochondrial superoxide production, 8-hydroxy-2-deoxyguanosine formation and neuronal loss in the rat hippocampus. Kainate-induced increases of mitochondrial superoxide production and hippocampal neuronal loss were attenuated in transgenic mice overexpressing mitochondrial superoxide dismutase-2.We propose that these results demonstrate a role for mitochondrial superoxide production in hippocampal pathology produced by kainate seizures. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.