Stress-induced activation of Nox contributes to cell survival signalling via production of hydrogen peroxide
Stress-induced activation of Nox contributes to cell survival signalling via production of hydrogen peroxide
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DOI：
10.1111/j.1471-4159.2009.06081.x
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发表时间：
2009-06-01
影响因子：
4.7
通讯作者：
Cotter, Thomas G.
中科院分区：
文献类型：
--
作者：
Groeger, Gillian;Mackey, Ashley M.;Cotter, Thomas G.
传统上，活性氧簇(ROS)被认为是一组有毒的分子；然而，最近的研究表明，这些分子，包括过氧化氢，也能强烈地促进细胞存活。尽管视网膜有很大的产生ROS的能力，但人们对这些分子的非线粒体来源，特别是参与直接产生超氧化物和间接产生H_2O_2的NADPH氧化酶(NOX)蛋白的表达和功能知之甚少。这项研究表明，视网膜来源的661W细胞和小鼠视网膜外植体表达NOX2、NOX4及其某些成熟的调节因子。用661W细胞测定了NOX2和NOX4在产生促进生存的过氧化氢中的作用，并确定了一些控制因素。为了确定这一现象是否与生理相关，建立了视网膜外植体中二氯荧光素荧光(由过氧化氢产生)的时移成像新技术，结果表明，外植体也会产生过氧化氢爆发。过氧化氢产量的增加部分地被Nox蛋白的抑制剂所阻断。总体而言，这项研究证明了NOX2和NOX4在视网膜来源的细胞中具有促进生存的作用，阐明了一些调节机制，并揭示了类似的现象在整个视网膜组织中存在。
Reactive oxygen species (ROS) have traditionally been viewed as a toxic group of molecules; however, recent publications have shown that these molecules, including H2O2, can also strongly promote cell survival. Even though the retina has a large capacity to produce ROS, little is known about its non-mitochondrial sources of these molecules, in particular the expression and function of NADPH oxidase (Nox) proteins which are involved in the direct generation of superoxide and indirectly H2O2. This study demonstrated that 661W cells, a retina-derived cell line, and mouse retinal explants express Nox2, Nox4 and certain of their well-established regulators. The roles of Nox2 and Nox4 in producing pro-survival H2O2 were determined using 661W cells and some of the controlling factors were identified. To ascertain if this phenomenon could have physiological relevance, the novel technique of time-lapse imaging of dichlorofluorescein fluorescence (generated upon H2O2 production) in retinal explants was established and it showed that explants also produce a burst of H2O2. The increase in H2O2 production was partly blocked by an inhibitor of Nox proteins. Overall, this study demonstrates a pro-survival role of Nox2 and Nox4 in retina-derived cells, elucidates some of the regulatory mechanisms and reveals that a similar phenomenon exists in retinal tissue as a whole.