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首页> 外文期刊>Redox report: communications in free radical research >Hydrogen peroxide induces GADD153 in Jurkat cells through the protein kinase C-dependent pathway
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Hydrogen peroxide induces GADD153 in Jurkat cells through the protein kinase C-dependent pathway

机译：过氧化氢通过蛋白激酶C依赖性途径在Jurkat细胞中诱导GADD153

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摘要

Growth arrest and DNA damage-inducible gene 153 (GADD153) is a CCAAT/enhancer binding protein (C/EBP) related gene and is induced in response to various stimuli including DNA damaging agents, UV irradiation, and serum starvation. In this study, we investigated which intracellular signals contribute to the expression of GADD153 mRNA in Jurkat cells in response to oxidative stress using several kinds of kinase inhibitors. GADD153 mRNA expression was immediately enhanced following hydrogen peroxide exposure and was significantly inhibited by treatment with H-7, staurosporin, and Ro-31-8220. In particular, rottlerin, a PKC5 specific inhibitor, markedly attenuated hydrogen peroxide-induced GADD153 mRNA expression even at 1 (iM. Treatment with a potent PKC activator, phorbol-12-myristate-13-acetate (PMA), augmented GADD153 mRNA in Jurkat cells in the presence of hydrogen peroxide, although PMA alone induced GADD153 mRNA marginally. Hydrogen peroxide significantly enhanced the AP-1 binding activity of the nuclear extract from Jurkat cells to the GADD153 AP-1 binding site. AP-1 binding activity was suppressed by rottlerin treatment. These findings indicate that PKC, especially PKC8, plays an important role in the induction of GADD153 mRNA following oxidative stress.
机译：生长停滞和DNA损伤诱导基因153（GADD153）是与CCAAT /增强子结合蛋白（C / EBP）相关的基因，可响应各种刺激（包括DNA损伤剂，紫外线照射和血清饥饿）而被诱导。在这项研究中，我们调查了使用几种激酶抑制剂响应氧化应激，哪些细胞内信号有助于Jurkat细胞中GADD153 mRNA的表达。 GADD153 mRNA表达在过氧化氢暴露后立即增强，并被H-7，星形孢菌素和Ro-31-8220处理显着抑制。尤其是，PKC5特异性抑制剂rottlerin即使在1（iM。用有效的PKC激活剂phorbol-12-肉豆蔻酸酯13-乙酸酯（PMA）处理，也显着减弱了过氧化氢诱导的GADD153 mRNA表达，从而在Jurkat中增加了GADD153 mRNA的表达过氧化氢存在下，虽然PMA单独诱导了GADD153 mRNA的表达，但过氧化氢显着增强了Jurkat细胞核提取物与GADD153 AP-1结合位点的AP-1结合活性，但AP-1结合活性却受到抑制。这些发现表明，PKC，尤其是PKC8，在氧化应激后在诱导GADD153 mRNA中起重要作用。

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