Genetic Responses to Free Radicals: Homeostasis and Gene Control
Genetic Responses to Free Radicals: Homeostasis and Gene Control
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DOI：
10.1111/j.1749-6632.2000.tb06177.x
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发表时间：
2000-01
影响因子：
5.2
通讯作者：
B. González-Flecha;B. Demple
中科院分区：
文献类型：
--
作者：
B. González-Flecha;B. Demple
摘要：基因调控机制已经进化，允许细胞微调内源性氧化应激水平，并应对来自外部来源的增加的自由基。在大肠杆菌中，过氧化氢的水平由OxyR严格控制，OxyR被过氧化氢激活，以增加清除活性，并通过呼吸链限制过氧化氢的产生。亚微摩尔水平的过氧化氢在哺乳动物组织中保持不变，尽管控制这一控制的调控系统尚不清楚。过量的超氧化物在大肠杆菌中触发SoxRS系统，该系统由SoxR蛋白对氧化剂敏感的铁硫中心控制。一氧化氮通过铁硫中心的不同修饰来激活SoxR。SOXRS调节子动员多种功能来清除自由基和修复大分子中的氧化损伤，以及其他将许多环境因子排除在细胞外的机制。哺乳动物细胞也感知和响应亚毒性水平的一氧化氮，通过稳定其mRNA来激活血红素加氧酶1的表达。这些诱导在神经元和其他类型的细胞中引起对一氧化氮的适应性抵抗。
Abstract: Gene regulation mechanisms have evolved allowing cells to fine‐tune the level of “endogenous” oxidative stress and to cope with increased free radicals from external sources. Levels of H2O2 are tightly controlled in E. coli by OxyR, which is activated by H2O2 to increase scavenging activities and limit H2O2 generation by the respiratory chain. Sub‐micromolar levels of H2O2 are maintained in mammalian tissues, though the regulatory systems that govern this control are unknown. Excess superoxide triggers the soxRS system in E. coli, which is controlled by the oxidant‐sensitive iron‐sulfur centers of the SoxR protein. Nitric oxide activates SoxR by a different modification of the iron‐sulfur centers. The soxRS regulon mobilizes diverse functions to scavenge free radicals and repair oxidative damage in macromolecules, and other mechanisms that exclude many environmental agents from the cell. Mammalian cells also sense and respond to sub‐toxic levels of nitric oxide, activating expression of heme oxygenase 1 through stabilization of its mRNA. These inductions give rise to adaptive resistance to nitric oxide in neuronal and other cell types.