Mammalian antioxidant Defenses are not inducible by H2O2
Mammalian antioxidant Defenses are not inducible by H2O2
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DOI：
10.1074/jbc.m401888200
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发表时间：
2004-07-23
影响因子：
4.8
通讯作者：
Toledano, MB
中科院分区：
文献类型：
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作者：
Desaint, S;Luriau, S;Toledano, MB
作为了解哺乳动物如何调节细胞内 H2O2 浓度以防止其毒性的一种方法，我们分析了用无毒 H2O2 浓度处理后人类细胞的全基因组 mRNA 谱变化。我们发现了诱导和抑制基因的大量且基本上较晚的 H2O2 反应，这些基因出乎意料地包含很少或不包含抗氧化剂，但主要包含细胞凋亡和细胞周期控制活性。 p53 调节剂需要调节大约三分之一的 H2O2 刺激，并且缺乏与总细胞 H2O2 清除活性相关的增强，进一步表明 H2O2 会引发应激抗增殖/修复反应，但不会增加抗氧化防御。我们得出的结论是，哺乳动物的抗氧化防御是组成型的，这一发现与微生物中此类防御的氧化诱导能力形成鲜明对比。这一发现对于理解 H2O2 作为哺乳动物关键信号分子的作用可能很重要。
As an approach to understanding how mammals regulate H2O2 intracellular concentration to prevent its toxicity, we analyzed the genome-wide mRNA profile changes of human cells after treatment with a non-toxic H2O2 concentration. We identified a large and essentially late H2O2 response of induced and repressed genes that unexpectedly comprise few or no antioxidants but mostly apoptosis and cell cycle control activities. The requirement of the p53 regulator for regulating about a third of this H2O2 stimulon and the lack of an associated enhancement of total cellular H2O2 scavenging activity further suggest that H2O2 elicits a stress antiproliferative/ repair response that does not increase antioxidant defenses. We conclude that mammalian antioxidant defenses are constitutive, a finding that contrasts with the oxidant-inducibility of such defenses in microorganisms. This finding might be important in understanding the role of H2O2 as a key signaling molecule in mammals.