Oxygen-sensing mechanisms and the regulation of redox-responsive transcription factors in development and pathophysiology.
Oxygen-sensing mechanisms and the regulation of redox-responsive transcription factors in development and pathophysiology.
复制标题
DOI：
10.1186/rr190
复制
发表时间：
2002
影响因子：
5.8
通讯作者：
Haddad JJ
中科院分区：
文献类型：
--
作者：
Haddad JJ
生物体如何感知环境中的氧气量，并在氧气水平下降时做出适当的反应？氧传感器及其背后的分子策略一直是无数研究的焦点，这些研究试图找到以下问题的答案：“氧传感器的身份是什么？“pO 2的动态变化构成了一种潜在的信号机制，用于调节还原-氧化（氧化还原）敏感性和氧响应性转录因子、凋亡信号分子和炎性细胞因子的表达和激活。从胎盘呼吸到基于肺的呼吸的转变引起相对高氧转变或氧化应激，围产期发育中的肺在出生期间经历。特别是Δ pO 2的这种变化，差异性地调节转录因子缺氧诱导因子-1 α（HIF-1α）和核因子-κB（NF-κB）的区室化和功能。此外，氧诱导的HIF-1α和NF-κB的调节与细胞内氧化还原状态密切相关，因此调节氧化还原平衡会影响它们在分子水平上的反应性（表达/反式激活）。HIF-1α和NF-κB在体外的差异调节是由氧敏感性和氧化还原依赖性途径控制的，这些途径在从胎盘呼吸到子宫外肺呼吸的转变过程中控制这些因子的调节。出生过渡期在体内和子宫外也以氧化还原依赖性方式调节凋亡信号通路，这与NF-κB被转录调节以发挥抗凋亡功能一致。在氧化应激条件和病理生理学中炎症状态的增强之间建立了关联，其由氧和氧化还原敏感性多效性细胞因子调节。
How do organisms sense the amount of oxygen in the environment and respond appropriately when the level of oxygen decreases? Oxygen sensing and the molecular stratagems underlying the process have been the focus of an endless number of investigations trying to find an answer to the question: "What is the identity of the oxygen sensor?" Dynamic changes in pO2 constitute a potential signaling mechanism for the regulation of the expression and activation of reduction-oxidation (redox)-sensitive and oxygen-responsive transcription factors, apoptosis-signaling molecules and inflammatory cytokines. The transition from placental to lung-based respiration causes a relatively hyperoxic shift or oxidative stress, which the perinatal, developing lung experiences during birth. This variation in ΔpO2, in particular, differentially regulates the compartmentalization and functioning of the transcription factors hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-κB (NF-κB). In addition, oxygen-evoked regulation of HIF-1α and NF-κB is closely coupled with the intracellular redox state, such that modulating redox equilibrium affects their responsiveness at the molecular level (expression/transactivation). The differential regulation of HIF-1α and NF-κB in vitro is paralleled by oxygen-sensitive and redox-dependent pathways governing the regulation of these factors during the transition from placental to lung-based respiration ex utero. The birth transition period in vivo and ex utero also regulates apoptosis signaling pathways in a redox-dependent manner, consistent with NF-κB being transcriptionally regulated in order to play an anti-apoptotic function. An association is established between oxidative stress conditions and the augmentation of an inflammatory state in pathophysiology, regulated by the oxygen- and redox-sensitive pleiotropic cytokines.
登录
查看更多内容
影响因子：
5.5
作者：
Baines, DL;Ramminger, SJ;Wilson, SM
通讯作者：
Wilson, SM
DOI：
10.1165/ajrcmb.19.4.3173
发表时间：
1998-10-01
影响因子：
6.4
作者：
Barazzone, C;Horowitz, S;Piguet, PF
通讯作者：
Piguet, PF
影响因子：
5.9
作者：
BERNARD, GR
通讯作者：
BERNARD, GR
影响因子：
7.4
作者：
Anuradha, CD;Kanno, S;Hirano, S
通讯作者：
Hirano, S
影响因子：
4.8
作者：
Budinger, GRS;Duranteau, J;Schumacker, PT
通讯作者：
Schumacker, PT