SvfI inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae
SvfI inhibits reactive oxygen species generation and promotes survival under conditions of oxidative stress in Saccharomyces cerevisiae
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作者：
Brace, JL;VanderWeele, DJ;Rudin, CM
细胞凋亡或程序性细胞死亡的异常调节是几种疾病的病因，包括癌症、免疫缺陷和神经退行性疾病。我们假设哺乳动物细胞死亡调控的关键特征可能在单细胞生物中是保守的，如芽殖酵母酿酒酵母。我们先前在一个突变筛选中鉴定了酵母基因SVF 1，该突变可以通过外源表达人抗凋亡基因Bcl-x（L）在功能上得到补充。抗凋亡Bcl-2家族成员已显示通过上调哺乳动物细胞中的抗氧化剂途径来促进氧化还原稳定性。在这里，我们证明了Svf 1蛋白是酵母生存所需的氧化应激条件下，包括冷应激。缺乏SVF 1的细胞对与活性氧（ROS）产生增加相关的条件和ROS的直接化学前体过敏，并且在这些条件下表现出ROS水平增加。对氧化应激的超敏反应可以通过抗氧化剂N-乙酰半胱氨酸或外源SVF 1的表达来逆转，尽管Bcl-x（L）的外源表达不能保护细胞免受冷应激。哺乳动物细胞中的外源SVF 1表达赋予对H2 O2暴露的抗性。我们的数据与以前的观察结果一致，表明氧化应激反应在哺乳动物细胞凋亡调控中起关键作用，并验证了S。酿酒酵母作为研究程序性细胞死亡的模型。版权所有（c）2005年约翰威利父子有限公司。
Aberrant regulation of apoptosis, or programmed cell death, contributes to the aetiology of several diseases, including cancers, immunodeficiencies and neurodegenerative illnesses. We hypothesized that key features of mammalian cell death regulation may be conserved in single celled organisms such as the budding yeast Saccharomyces cerevisiae. We previously identified the yeast gene SVF1 in a screen for mutations that could be functionally complemented by exogenous expression of the human antiapoptotic gene Bcl-x(L). Anti-apoptotic Bcl-2 family members have been shown to promote redox stability through upregulation of antioxidant pathways in mammalian cells. Here we demonstrate that the Svf1 protein is required for yeast survival under conditions of oxidative stress, including cold stress. Cells lacking SVF1 are hypersensitive to conditions associated with increased reactive oxygen species (ROS) generation and to direct chemical precursors of ROS, and demonstrate increased levels of ROS under these conditions. Hypersensitivity to oxidative stress can be reversed by treatment with the antioxidant N-acetylcysteine or expression of exogenous SVF1, although exogenous expression of Bcl-x(L) did not protect cells from cold stress. Exogenous SVF1 expression in mammalian cells confers resistance to H2O2 exposure. Our data are consistent with previous observations suggesting a key role of oxidative stress response in mammalian apoptotic regulation and validate the use of S. cerevisiae as a model for studying programmed cell death. Copyright (c) 2005 John Wiley & Sons, Ltd.