Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2.
Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2.
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DOI：
10.1152/physrev.00030.2011
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发表时间：
2012-07
影响因子：
33.6
通讯作者：
Semenza GL
中科院分区：
文献类型：
--
作者：
Prabhakar NR;Semenza GL
缺氧是影响细胞、组织、器官和生理系统的基本刺激。缺氧诱导因子-1（HIF-1）的发现以及随后对HIF家族转录激活因子其他成员的鉴定为氧稳态的分子基础提供了深入的了解。本文综述了低氧诱导因子的激活机制及其在低氧生理和病理生理反应中的作用，重点是心肺系统。HIF是由O2调节的HIF-1α或HIF-2α亚基和组成型表达的HIF-1β亚基组成的异二聚体。在氧可用性降低的条件下诱导HIF活性需要稳定HIF-1α和HIF-2α，这是由于脯氨酰羟基化降低、与HIF-1β的二聚化以及由于天冬酰胺酰羟基化降低而与辅活化剂的相互作用。除缺氧外的刺激，如一氧化氮和活性氧，也可以激活HIF。HIF-1和HIF-2对于颈动脉体的急性O2感知是必不可少的，并且它们的协调转录激活对于慢性缺氧的生理适应（包括红细胞生成、血管形成、代谢重编程和消化性适应）是至关重要的。相反，与睡眠呼吸障碍相关的间歇性缺氧导致HIF-1α和HIF-2α之间的失衡，引起氧化应激，导致心肺病理学。
Hypoxia is a fundamental stimulus that impacts cells, tissues, organs, and physiological systems. The discovery of hypoxia-inducible factor-1 (HIF-1) and subsequent identification of other members of the HIF family of transcriptional activators has provided insight into the molecular underpinnings of oxygen homeostasis. This review focuses on the mechanisms of HIF activation and their roles in physiological and pathophysiological responses to hypoxia, with an emphasis on the cardiorespiratory systems. HIFs are heterodimers comprised of an O2-regulated HIF-1α or HIF-2α subunit and a constitutively expressed HIF-1β subunit. Induction of HIF activity under conditions of reduced O2 availability requires stabilization of HIF-1α and HIF-2α due to reduced prolyl hydroxylation, dimerization with HIF-1β, and interaction with coactivators due to decreased asparaginyl hydroxylation. Stimuli other than hypoxia, such as nitric oxide and reactive oxygen species, can also activate HIFs. HIF-1 and HIF-2 are essential for acute O2 sensing by the carotid body, and their coordinated transcriptional activation is critical for physiological adaptations to chronic hypoxia including erythropoiesis, vascularization, metabolic reprogramming, and ventilatory acclimatization. In contrast, intermittent hypoxia, which occurs in association with sleep-disordered breathing, results in an imbalance between HIF-1α and HIF-2α that causes oxidative stress, leading to cardiorespiratory pathology.
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影响因子：
5.3
作者：
Bishop, Tammie;Gallagher, Denis;Ratcliffe, Peter J.
通讯作者：
Ratcliffe, Peter J.
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
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Zheng, Yong Tang
影响因子：
2.3
作者：
Baby, SM;Roy, A;Lahiri, S
通讯作者：
Lahiri, S
影响因子：
11.2
作者：
Aprelikova, Olga;Wood, Matthew;Barrett, J. Carl
通讯作者：
Barrett, J. Carl
影响因子：
16
作者：
Bakker, Walbert J.;Harris, Isaac S.;Mak, Tak W.
通讯作者：
Mak, Tak W.