Cellular regulation by hydrogen peroxide
Cellular regulation by hydrogen peroxide
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DOI：
10.1097/01.asn.0000077404.45564.7e
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发表时间：
2003-08-01
影响因子：
13.6
通讯作者：
Kang, SW
中科院分区：
文献类型：
--
作者：
Rhee, SG;Chang, TS;Kang, SW
大量证据表明，H2O2 的瞬时产生是由各种细胞表面受体激活引发的重要信号事件。了解 H2O2 的细胞内信使功能需要研究受体占据如何引发 H2O2 的产生、产生的 H2O2 靶向哪些类型的分子以及 H2O2 在完成其使命后如何被消除。最近的研究表明，生长因子诱导的 H2O2 产生需要激活 PtdIns 3-激酶。 PtdIns 3-激酶的重要作用可能是提供 PI(3,4,5)P-3，招募并激活 Rac 的鸟嘌呤核苷酸交换因子，这是激活 NADPH 氧化酶所需的。 H2O2 作用的目标包括含有反应性 Cys 残基的蛋白质。因此，响应生长因子而产生的 H2O2 通过特异性氧化催化性半胱氨酸，导致各种细胞中蛋白质酪氨酸磷酸酶失活。这些结果与其他观察结果一起表明，通过结合相应的生长因子而激活受体酪氨酸激酶本身可能不足以增加细胞中蛋白质酪氨酸磷酸化的稳态水平。相反，可能还需要 H2O2 同时抑制蛋白酪氨酸磷酸酶。过氧化还原蛋白是新发现的过氧化物酶家族的成员，可有效降低用各种细胞表面配体刺激的细胞中产生的细胞内 H2O2 水平。此外，与许多其他细胞内信使代谢酶的情况一样，过氧化还原蛋白酶的活性似乎是通过蛋白质磷酸化来调节的。
Substantial evidence suggests that the transient production of H2O2 is an important signaling event triggered by the activation of various cell surface receptors. Understanding the intracellular messenger function of H2O2 calls for studies of how receptor occupation elicits the production of H2O2, what kinds of molecules are targeted by the produced H2O2, and how H2O2 is eliminated after the completion of its mission. Recent studies suggest that growth factor-induced H2O2 production requires the activation of PtdIns 3-kinase. The essential role of PtdIns 3-kinase is likely to provide PI(3,4,5)P-3 that recruits and activates a guanine nucleotide exchange factor of Rac, which is required for the activation of NADPH oxidase. The targets of H2O2 action include proteins that contain a reactive Cys residue. Thus, H2O2 produced in response to growth factor causes inactivation of protein tyrosine phosphatases in various cells by oxidizing specifically the catalytic Cys. These results, together with other observations, indicate that the activation of a receptor tyrosine kinase per se by binding of the corresponding growth factor might not be sufficient to increase the steady-state level of protein tyrosine phosphorylation in cells. Rather, the concurrent inhibition of protein tyrosine phosphatases by H2O2 might also be required. Peroxiredoxins, members of a newly discovered family of peroxidases, efficiently reduced the intracellular level of H2O2 produced in the cells stimulated with various cell surface ligands. Furthermore, the activity of peroxiredoxin enzymes seems to be regulated via protein phosphorylation as in the case of many other intracellular messenger metabolizing enzymes.