Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction
Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction
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DOI：
10.1152/ajpcell.00298.2009
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发表时间：
2010-06-01
影响因子：
5.5
通讯作者：
Ali, Sameh S.
中科院分区：
文献类型：
--
作者：
Douglas, Robert M.;Ryu, Julie;Ali, Sameh S.
李建军，李建军，李建军，李建军，等。线粒体功能障碍对间歇性缺氧/高碳酸血症患者神经细胞凋亡的影响。[J] .中国生物医学工程学报，2016,32(2):559 - 563。首次发表于2010年3月31日；doi: 10.1152 / ajpcell.00298.2009。-呼吸障碍状态，如阻塞性睡眠呼吸暂停，其本质上是周期性的，被认为会诱发儿童和成人人群的神经认知疾病。间歇性缺氧的振荡性质，特别是慢性缺氧，可能模仿缺血-再灌注的模式，即组织和细胞暴露于低氧和高氧的发作，这可能导致氧化应激。因此，我们决定在我们的间歇性缺氧/高碳酸血症动物模型中探索氧化应激的潜在贡献以及线粒体在这种应激中可能发挥的作用。新生小鼠暴露于间歇性缺氧/高碳酸血症10天和2周。间歇性缺氧/高碳酸血症导致大脑皮层凋亡细胞死亡明显增加。对间歇性缺氧/高碳酸血症暴露的大脑中分离线粒体的耗氧量研究表明，状态4和状态3的呼吸活动分别显著减少了60%和75%。电子顺磁共振波谱显示，在非磷酸化状态4期间，超氧化物的产生显著增加了37%，尽管状态3期间的超氧化物泄漏在处理后没有增加。暴露动物的神经元超氧化物特异性二氢乙啶氧化也更大。这些研究表明，间歇性缺氧/高碳酸血症由于小鼠中枢神经系统的线粒体反应而导致氧化应激。
Douglas RM, Ryu J, Kanaan A, Rivero M, Dugan LL, Haddad GG, Ali SS. Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction. Am J Physiol Cell Physiol 298: C1594-C1602, 2010. First published March 31, 2010; doi:10.1152/ajpcell.00298.2009.-Breathing-disordered states, such as in obstructive sleep apnea, which are cyclical in nature, have been postulated to induce neurocognitive morbidity in both pediatric and adult populations. The oscillatory nature of intermittent hypoxia, especially when chronic, may mimic the paradigm of ischemia-reperfusion in that tissues and cells are exposed to episodes of low and high O(2) and this may lead to oxidant stress. Therefore, we decided to explore the potential contribution of oxidant stress in our intermittent hypoxia/hypercapnia animal model and the role that mitochondria might play in this stress. Neonatal mice were exposed to intermittent hypoxia/hypercapnia for 10 days and 2 wk. Combined intermittent hypoxia/hypercapnia led to a marked increase in apoptotic cell death in the cerebral cortex. Oxygen consumption studies in isolated mitochondria from intermittent hypoxia/hypercapnia-exposed brains demonstrated significant reductions in both state 4 and state 3 respiratory activities by similar to 60% and 75%, respectively. Electron paramagnetic resonance spectroscopy registered a significant increase in superoxide production during nonphosphorylating state 4 by 37%, although superoxide leakage during state 3 did not increase upon treatment. Neuronal superoxide-specific dihydroethidium oxidation was also greater in exposed animals. These studies indicate that intermittent hypoxia/hypercapnia leads to oxidative stress due to mitochondrial response within the mouse central nervous system.