Center for Systems Biology of O2 Sensing, Department of Medicine, University of Chicago, IL 60637, USA.
Respir Physiol Neurobiol. 2010 Dec 31;174(3):230-4. doi: 10.1016/j.resp.2010.08.022. Epub 2010 Sep 8.
Carotid bodies and neonatal adrenal medullary chromaffin cells (AMC) respond rapidly to acute hypoxia before compromising cellular functions. Responses to acute hypoxia are dynamically altered by chronic perturbations in arterial blood O2 levels resulting from breathing disorders. Sleep disordered breathing with recurrent apneas cause periodic decreases in arterial blood O2 or intermittent hypoxia (IH). Recent studies suggest that reactive oxygen species (ROS) mediate cellular adaptations to prolonged hypoxia. In this article we discuss the evidence for ROS in mediating exaggerated carotid body and AMC responses to acute hypoxia by IH and the underlying cellular and molecular mechanisms. IH increases ROS levels, and anti-oxidants prevent IH-induced augmented responses of the carotid body and AMC to hypoxia. The enhanced hypoxic sensitivity by IH involves ROS-dependent recruitment of transmitters/modulators in the carotid body and Ca2+ signaling mechanisms in AMC. Mechanisms by which IH elevates ROS include activation of NADPH oxidases, inhibition of mitochondrial complex I activity and down-regulation of anti-oxidant enzymes. Transcriptional regulation of pro- and anti-oxidant enzymes by hypoxia-inducible factors 1 and 2 appears to be a major molecular mechanism regulating ROS generation by IH.
颈动脉体和新生儿肾上腺髓质嗜铬细胞（AMC）在细胞功能受损之前，对急性缺氧迅速作出反应。由于呼吸障碍导致动脉血氧水平的慢性波动，急性缺氧的反应会发生动态变化。睡眠呼吸障碍伴反复发作的呼吸暂停会导致动脉血氧周期性下降或间歇性缺氧（IH）。最近的研究表明，活性氧（ROS）介导细胞对长时间缺氧的适应性。本文讨论了 ROS 在介导 IH 引起的颈动脉体和 AMC 对急性缺氧反应过度中的作用，以及潜在的细胞和分子机制。IH 增加了 ROS 水平，抗氧化剂可防止 IH 引起的颈动脉体和 AMC 对缺氧反应的增强。IH 增强的低氧敏感性涉及 ROS 依赖性募集颈动脉体中的递质/调节剂以及 AMC 中的 Ca2+信号机制。IH 升高 ROS 的机制包括 NADPH 氧化酶的激活、线粒体复合物 I 活性的抑制和抗氧化酶的下调。缺氧诱导因子 1 和 2 对促氧化剂和抗氧化酶的转录调节似乎是调节 IH 产生 ROS 的主要分子机制。
