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首页> 外文期刊>Molecular and Cellular Biology >Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress
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Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress

机译：人OGG1活性对细胞氧化应激反应的氧化还原调节。

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8-Oxoguanine (8-oxoG), a common and mutagenic form of oxidized guanine in DNA, is eliminated mainly through base excision repair. In human cells its repair is initiated by human OGG1 (hOGG1), an 8-oxoG DNA glycosylase. We investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the hOGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was abolished by cadmium and could not be recovered by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts were modulated by cysteine-modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmium-treated cells. These results suggest that cadmium inhibits hOGG1 activity mainly by indirect oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active hOGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity.
机译：8-氧鸟嘌呤（8-oxoG）是DNA中氧化鸟嘌呤的一种常见诱变形式，主要通过碱基切除修复来消除。在人类细胞中，其修复是由人类OGG1（hOGG1）（一种8-oxoG DNA糖基化酶）启动的。我们调查了人类淋巴母细胞急性镉暴露对hOGG1活性的影响。我们显示，与氧化还原细胞状态的改变相吻合，hOGG1的8-oxoG DNA糖基化酶活性几乎被完全抑制。但是，一旦氧化还原细胞状态恢复正常，hOGG1活性就会恢复正常水平。在体外，纯化的hOGG1的活性被镉消除，而EDTA无法回收。然而，在细胞中，镉对OGG1活性的可逆失活与蛋白质的可逆氧化严格相关。此外，纯化的OGG1和粗提物的8-oxoG DNA糖基化酶活性被半胱氨酸修饰剂调节。 OGG1被硫醇氧化剂二酰胺氧化导致抑制活性和类似于镉处理细胞中所见的蛋白质迁移模式。这些结果表明，镉主要通过关键半胱氨酸残基的间接氧化来抑制hOGG1的活性，并且金属从细胞中的排出导致氧化还原细胞状态的正常化和活性hOGG1的恢复。本文介绍的结果揭示了一种新颖的氧化还原依赖性机制，可调节OGG1的活性。

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