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[一氧化氮诱导的基因表达的氧化还原依赖性调控]

[Redox-dependent regulation of gene expression induced by nitric oxide].

作者信息

Turpaev K T, Litvinov D Iu

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.

出版信息

Mol Biol (Mosk). 2004 Jan-Feb;38(1):56-68.

Abstract

Nitric oxide (NO) is a mobile, highly reactive signal molecule, and changes the expression of specific genes in effector cells. Under physiological conditions, NO reacts with molecular oxygen and with reactive oxygen species (ROS) to produce intermediates known as reactive nitrogen species (RNS). The production of NO and RNS in the cell is controlled by hormones, neurotransmitters, cytokines, and growth factors. Hence NO and its derivatives act as secondary paracrinous factors and transmit the signal from NO-producing to neighboring cells. Intracellular reception of NO and RNS is due to Src-related tyrosine protein kinases, G-protein Ras, cytochrome oxidase, and guanylate cyclase. Receptor proteins mostly contain heme, active thiol, or iron-sulfur groups, and are both on the plasma membrane and in internal cell compartments. Many of the NO receptors are the key components of cell regulatory systems controlling the transcription factors AP-1, HIF-1, NF-kappa B, and p53 and the expression of their target genes. A distinguishing feature of NO signaling is that changes in redox potential of the cell switch the NO receptor and, consequently, modify the NO effect. Depending on the ROS level, NO activates different signal transduction pathways to induce (or suppress) different gene sets. The data considered indicate that antioxidants may be used to directionally change the transcriptional response of the cell to NO.

摘要

一氧化氮(NO)是一种可移动的、高反应性的信号分子,能改变效应细胞中特定基因的表达。在生理条件下,NO与分子氧和活性氧(ROS)反应生成称为活性氮物种(RNS)的中间体。细胞内NO和RNS的产生受激素、神经递质、细胞因子和生长因子控制。因此,NO及其衍生物作为次级旁分泌因子,将信号从产生NO的细胞传递至邻近细胞。细胞内对NO和RNS的接收归因于Src相关酪氨酸蛋白激酶、G蛋白Ras、细胞色素氧化酶和鸟苷酸环化酶。受体蛋白大多含有血红素、活性硫醇或铁硫基团,存在于质膜和细胞内区室中。许多NO受体是控制转录因子AP-1、HIF-1、NF-κB和p53及其靶基因表达的细胞调节系统的关键组成部分。NO信号传导的一个显著特征是细胞氧化还原电位的变化会切换NO受体,从而改变NO的作用。根据ROS水平,NO激活不同的信号转导途径以诱导(或抑制)不同的基因集。所考虑的数据表明,抗氧化剂可用于定向改变细胞对NO的转录反应。

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