Comparing nitrosative versus oxidative stress toward zinc ringer-dependent transcription.: Unique role for NO.
Comparing nitrosative versus oxidative stress toward zinc ringer-dependent transcription.: Unique role for NO.
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DOI：
10.1074/jbc.m111216200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Sies, H
中科院分区：
文献类型：
--
作者：
Kröncke, KD;Klotz, LO;Sies, H
在炎症反应期间，细胞处于亚硝化和/或氧化应激下。锌指转录因子维生素D受体（VDR）和类维生素A X受体（RXR）被用作表征NO和/或活性氧对锌指依赖性基因表达的影响的模型系统。一氧化氮（NO.）以及H2 O2、单线态氧（O-1（2））、过氧自由基（ROO.）和过氧亚硝酸根（ONOO-）分别以剂量依赖性方式抑制VDR/RXR-DNA复合物的形成。NO对VDR/RXR-DNA复合物形成的抑制作用可被二硫苏糖醇完全恢复，而H_2O_2的抑制作用仅部分可逆，O-1（2），ROO的抑制作用可被完全恢复。或ONOO-是不可逆的。在瞬时转染VDR和RXR的细胞中，亚毒性浓度的NO或过氧化氢和细胞内产生的超氧阴离子自由基抑制VDR/RXR依赖性报告基因活性的剂量依赖性方式。有趣的是，在亚硝化应激后，细胞可以修复VDR和RXR的锌指，但在氧化应激后不能。结果表明，在所研究的反应性物种中，只有NO.可以足够温和地被认为是一种调节剂，而不仅仅是通过锌指转录因子抑制基因表达。
During inflammatory reactions, cells are under nitrosative and/or oxidative stress. The zinc finger transcription factors vitamin D receptor (VDR) and retinoid X receptor (RXR) were used as a model system to characterize effects of NO. and/or reactive oxygen species on zinc finger-dependent gene expression. Nitric oxide (NO.) as well as H2O2, singlet oxygen (O-1(2)), peroxyl radicals (ROO.), and peroxynitrite (ONOO-), respectively, were shown to inhibit VDR/RXR-DNA complex formation in vitro in a dose-dependent manner. While NO-induced inhibition of VDR/RXR-DNA complex formation could be restored nearly completely by subsequent treatment with dithiothreitol, inhibition by H2O2 proved to be only partially reversible, and inhibition by O-1(2), ROO. or ONOO- was found to be irreversible. In cells transiently transfected with VDR and RXR, subtoxic concentrations of NO. or hydroperoxides and intracellular generation of superoxide anion radicals inhibited VDR/RXR-dependent reporter gene activity in a dose-dependent manner. Interestingly, cells can repair the zinc fingers of VDR and RXR after nitrosative stress but not after oxidative stress. The results indicate that, among the reactive species investigated, only NO. may act sufficiently gentle to be considered as a regulator and not only as an inhibitor of gene expression via zinc finger transcription factors.