H2O2-dependent activation of GCLC-ARE4 reporter occurs by mitogen-activated protein kinase pathways without oxidation of cellular glutathione or thioredoxin-1
H2O2-dependent activation of GCLC-ARE4 reporter occurs by mitogen-activated protein kinase pathways without oxidation of cellular glutathione or thioredoxin-1
复制标题
DOI：
10.1074/jbc.m307547200
复制
发表时间：
2004-02-13
影响因子：
4.8
通讯作者：
Jones, DP
中科院分区：
文献类型：
--
作者：
Go, YM;Gipp, JJ;Jones, DP
gp 91（phox）同源物Nox 1产生H2 O2，其诱导细胞生长、转化和致瘤性。然而，目前尚不清楚H2 O2的作用是否是通过通常的氧化细胞环境间接介导的，或者H2 O2是否更直接地靶向特定的信号通路。在这里，我们研究了信号H2 O2诱导的Nox 1过表达使用荧光素酶报告的抗氧化反应元件ARE 4。令人惊讶的是，Nox 1衍生的H2 O2激活报告基因15倍，对主要的巯基抗氧化物质，谷胱甘肽和硫氧还蛋白的氧化还原状态没有影响。H2 O2信号传导到ARE 4是通过激活Ras调节的c-Jun N-末端激酶和ERK 1/2途径介导的。因此，导致激酶信号传导途径的“氧化还原信号传导”不同于“氧化应激”，并且由离散的局部氧化还原电路介导。
The gp91(phox) homologue Nox1 produces H2O2, which induces cell growth, transformation, and tumorigenicity. However, it has not been clear whether H2O2 effects are mediated indirectly via a generally oxidizing cellular environment or whether H2O2 more directly targets specific signaling pathways. Here, we investigated signaling by H2O2 induced by Nox1 overexpression using a luciferase reporter regulated by the antioxidant response element ARE4. Surprisingly, Nox1-derived H2O2 activated the reporter gene 15-fold with no effect on the redox state of the major thiol antioxidant substances, glutathione and thioredoxin. H2O2 signaling to ARE4 was mediated by activation of both the c-Jun N-terminal kinase and ERK1/2 pathways modulated by Ras. Thus, "redox signaling" resulting in kinase signaling pathways is distinct from "oxidative stress," and is mediated by discrete, localized redox circuitry.