活性氧
细胞生物学
转录因子
调解人
氧化磷酸化
缺氧(环境)
细胞内
生物
信号转导
超氧化物
三磷酸腺苷
化学
生物化学
氧气
基因
酶
有机化学
作者
Andrea Zepeda,Adalberto Pessoa,Rodrigo Castillo,Carolina A. Figueroa,Víctor M. Pulgar,Jorge G. Farías
摘要
Reactive oxygen species such as superoxide anion radicals (O 2 − ) and hydrogen peroxide (H 2 O 2 ) have for long time been recognized as undesirable by‐products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast‐acting mechanisms acting within a wide range of partial pressures of oxygen (O 2 ). Intracellular O 2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia‐inducible factor 1 (HIF‐1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O 2 ‐dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF‐1 coordinately regulates tissue O 2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro‐oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF‐mediated O 2 sensing mechanisms and their interactions with reactive oxygen species–generating pathways in normal and abnormal physiology. Copyright © 2013 John Wiley & Sons, Ltd.
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