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首页> 外文期刊>The European Journal of Neuroscience >Hypoxia induces complex I inhibition and ultrastructural damage by increasing mitochondrial nitric oxide in developing CNS.
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Hypoxia induces complex I inhibition and ultrastructural damage by increasing mitochondrial nitric oxide in developing CNS.

机译：缺氧通过增加中枢神经系统中的线粒体一氧化氮诱导复合物I抑制和超微结构破坏。

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NO-mediated toxicity contributes to neuronal damage after hypoxia; however, the molecular mechanisms involved are still a matter of controversy. Since mitochondria play a key role in signalling neuronal death, we aimed to determine the role of nitrative stress in hypoxia-induced mitochondrial damage. Therefore, we analysed the biochemical and ultrastructural impairment of these organelles in the optic lobe of chick embryos after in vivo hypoxia-reoxygenation. Also, we studied the NO-dependence of damage and examined modulation of mitochondrial nitric oxide synthase (mtNOS) after the hypoxic event. A transient but substantial increase in mtNOS content and activity was observed at 0-2 h posthypoxia, resulting in accumulation of nitrated mitochondrial proteins measured by immunoblotting. However, no variations in nNOS content were observed in the homogenates, suggesting an increased translocation to mitochondria and not a general de novo synthesis. In parallel with mtNOS kinetics, mitochondria exhibited prolonged inhibition of maximal complex I activity and ultrastructural phenotypes associated with swelling, namely, fading of cristae, intracristal dilations and membrane disruption. Administration of the selective nNOS inhibitor 7-nitroindazole 20 min before hypoxia prevented complex I inhibition and most ultrastructural damage. In conclusion, we show here for the first time that hypoxia induces NO-dependent complex I inhibition and ultrastructural damage by increasing mitochondrial NO in the developing brain.
机译：NO介导的毒性导致缺氧后神经元的损害;然而，涉及的分子机制仍存在争议。由于线粒体在信号神经元死亡中起关键作用，因此我们旨在确定硝化应激在缺氧诱导的线粒体损伤中的作用。因此，我们分析了体内缺氧-复氧后雏鸡视神经叶中这些细胞器的生化和超微结构损伤。此外，我们研究了缺氧损伤后NO的依赖性，并研究了线粒体一氧化氮合酶（mtNOS）的调节。在缺氧后0-2小时观察到mtNOS含量和活性的短暂但显着增加，导致通过免疫印迹法测定的硝化线粒体蛋白积累。但是，在匀浆中未观察到nNOS含量的变化，这表明向线粒体的转运增加，而不是常规的从头合成。线粒体与mtNOS动力学同时显示出最大的复合物I活性和与肿胀相关的超结构表型的延长抑制，即cr的消退，晶体内扩张和膜破裂。缺氧前20分钟给予选择性nNOS抑制剂7-硝基吲唑可预防复合物I抑制和大多数超微结构损害。总之，我们在这里首次表明缺氧会通过增加发育中的脑线粒体NO来诱导NO依赖的复合物I抑制和超微结构损伤。

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