Role of nitric oxide in the radiation-induced bystander effect.
Role of nitric oxide in the radiation-induced bystander effect.
复制标题
一氧化氮在辐射引起的旁观者效应中的作用。
DOI：
10.1016/j.redox.2015.08.018
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发表时间：
2015-12
期刊：
影响因子：
11.4
通讯作者：
Yakovlev VA
中科院分区：
文献类型：
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作者：
Yakovlev VA
未受辐射但受辐射细胞释放的“应激信号因子”影响的细胞称为旁观者细胞。这些细胞，以及直接照射的细胞，表达DNA损伤相关蛋白，并显示过量的DNA损伤，染色体畸变，突变和恶性转化。自1992年Nagasawa和Little首次描述这一现象以来，在过去的20年里，人们对这一现象进行了广泛的研究，并将其称为辐射诱导的旁观者效应（里贝）。已经确定了几个因素在旁观者反应中起作用。本文就一氧化氮（NO）及其在里贝的刺激和增殖中的作用作一综述。NO的疏水特性允许其通过细胞质和质膜扩散，使得该信号分子容易地从照射的细胞扩散到旁观者细胞，而不涉及间隙连接细胞间通讯。在辐射组织中产生的NO通过许多调节蛋白的翻译后修饰介导细胞调节。这些修饰中研究最多的是S-亚硝基化（半胱氨酸的可逆氧化）和酪氨酸硝化。这些修饰可以上调或下调许多调节不同NO依赖性效应的蛋白质的功能。这些NO依赖性效应包括刺激基因组不稳定性（GI）和在旁观者细胞中积累DNA错误而没有直接的DNA损伤。电离辐射刺激一氧化氮（NO）的产生。NO通过抑制BRCA 1蛋白表达刺激基因组不稳定性。NO可以扩散并刺激旁观者细胞的基因组不稳定性。NO从细胞到细胞的传播产生了“增变因子场”。提出了“变更者文件”的定义。
Cells that are not irradiated but are affected by “stress signal factors” released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage. Ionizing radiation stimulates generation of nitric oxide (NO). NO stimulates genomic instability by inhibiting BRCA1 protein expression. NO can diffuse and stimulate genomic instability in the bystander cells. Propagation of NO from cell-to-cell creates a “mutator fields”. Definition of the “mutator filed” is proposed.