GENERATION OF HYDROGEN-PEROXIDE BY BRAIN MITOCHONDRIA - THE EFFECT OF REOXYGENATION FOLLOWING POSTDECAPITATIVE ISCHEMIA
GENERATION OF HYDROGEN-PEROXIDE BY BRAIN MITOCHONDRIA - THE EFFECT OF REOXYGENATION FOLLOWING POSTDECAPITATIVE ISCHEMIA
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DOI：
10.1016/0003-9861(89)90148-3
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发表时间：
1989-03-01
影响因子：
3.9
通讯作者：
DELMAESTRO, RF
中科院分区：
文献类型：
--
作者：
CINO, M;DELMAESTRO, RF
假设线粒体在完全性脑缺血损伤产生增加的超氧阴离子自由基和过氧化氢（H2 O2）后缺血再氧合的量已被测试。在大鼠脑线粒体中，琥珀酸支持过氧化氢的产生，而NADH连接的底物，苹果酸加谷氨酸，这样做只有在呼吸链抑制剂的存在下。琥珀酸支持过氧化氢的产生减少鱼藤酮和解偶联剂羰基氰间氯苯腙和增强抗霉素A和增加氧张力。当最大限度地还原时，NADH脱氢酶和电子传递链的泛醌-细胞色素B区域是H2 O2的来源。这些研究表明，脑线粒体中H2 O2生成的显著部分通过将还原当量从泛醌转移到电子传递链的NADH脱氢酶部分来进行。琥珀酸支持的H2 O2产生的线粒体从大鼠脑暴露于15分钟的断头缺血是90%低于对照制剂。与对照制剂中测得的H2 O2生成增加相比，缺血后线粒体制剂中不同氧分压对H2 O2生成的影响可以忽略不计。呼吸链抑制剂和氧张力对琥珀酸支持的H2 O2产生的影响的比较表明，在缺血过程中，反向电子转移的能力受损。这些数据不支持缺血后再氧合过程中线粒体自由基生成增加的假设。
The hypothesis that mitochondria damaged during complete cerebral ischemia generate increased amounts of superoxide anion radical and hydrogen peroxide (H2O2) upon postischemic reoxygenation has been tested. In rat brain mitochondria, succinate supported H2O2 generation, whereas NADH-linked substrates, malate plus glutamate, did so only in the presence of respiratory chain inhibitors. Succinate-supported H2O2 generation was diminished by rotenone and the uncoupler carbonyl cyanide m-chlorphenylhydrazone and enhanced by antimycin A and increased oxygen tensions. When maximally reduced, the NADH dehydrogenase and the ubiquinone-cytochrome b regions of the electron transport chain are sources of H2O2. These studies suggest that a significant portion of H2O2 generation in brain mitochondria proceeds via the transfer of reducing equivalents from ubiquinone to the NADH dehydrogenase portion of the electron transport chain. Succinate-supported H2O2 generation by mitochondria isolated from rat brain exposed to 15 min of postdecapitative ischemia was 90% lower than that of control preparations. The effect of varying oxygen tensions on H2O2generation by postischemic mitochondrial preparations was negligible compared with the increased H2O2 generation measured in control preparations. Comparison of the effects of respiratory chain inhibitors and oxygen tension on succinate-supported H2O2 generation suggests that the ability for reversed electron transfer is impaired during ischemia. These data do not support the hypothesis that mitochondrial free radical generation increases during postischemic reoxygenation.