COORDINATE REGULATION OF THE NONCLASSICAL GPX ENZYMES

描述：抗氧化剂提供抗氧化因子的保护 包括谷胱甘肽（GSH）依赖性酶。 暴露于氧化应激 诱导抗氧化酶，包括这些GSH依赖性酶。 详细 对酶的氧化诱导的生物化学研究已经 虽然已经完成，但对分子水平的调控知之甚少。 这一建议是针对非经典的监管 硒依赖性GSH过氧化物酶（ncGPXs）胃肠道（GPX 2）， 血浆相关（GPX 3）和磷脂氢过氧化物（GPX 4）。 响应 这些GPX基因和它们的调节蛋白对外源性氧化 压力将被表征。 研究包括结构表征 通过对ncGPXs基因的5和3个侧翼区进行测序，确定mRNA 起始位点和定位基础启动子区。 诱导型启动子 每个基因的区域将使用一系列5-缺失来鉴定。 启动子构建体和单独的正和负调控元件 通过功能和结构研究确定。 这些元素的反应 各种各样的氧化剂将被确定。 其他研究将调查 存在于5个细胞中的独特茎环元件的功能作用 所有GPX的非翻译区，通过使用一系列的小基因， 嵌合构建体，以确定是否所有的共同调控机制， GPX存在。 获得的关于《公约》管理机制的资料 酶可用于研究它们在各种人类疾病中的保护作用。 疾病和环境毒素，以及确定是否常见 所有GSH依赖性酶都存在调节机制。

DESCRIPTION: Protection against oxidant factors is provided by antioxidants including glutathione (GSH)-dependent enzymes. Exposure to oxidative stress induces antioxidant enzymes including these GSH-dependent enzymes. Detailed biochemical studies on the oxidative induction of enzymes has been accomplished, yet little is known about regulation at a molecular level. This proposal is directed toward regulation of the nonclassical selenium-dependent GSH peroxidases (ncGPXs) gastrointestinal (GPX2), plasma-associated (GPX3), and phospholipid hydroperoxide (GPX4). Response of these GPX genes and their regulatory proteins to exogenous oxidative stress will be characterized. Studies include structural characterization of ncGPXs genes by sequencing 5 and 3 flanking regions, determining mRNA initiation sites, and locating basal promoter regions. Inducible promoter regions of each gene will be identified using a series of 5-deletion promoter constructs and individual positive and negative regulatory elements identified by functional and structural studies. Response of these elements to a variety of oxidants will be determined. Other studies will investigate the functional role of a unique stem-loop element present in the 5 untranslated regions of all GPXs through use of a series of mini-gene and chimeric constructs, to determine if a regulatory mechanism common to all GPXs exists. Information obtained about the regulatory mechanism of the enzymes can be used to study their protective role in a variety of human diseases and against environmental toxins, as well as determine if common regulatory mechanism(s) exist for all GSH-dependent enzymes.