Nitrosative stress-induced S-glutathionylation of protein disulfide isomerase.
Nitrosative stress-induced S-glutathionylation of protein disulfide isomerase.
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DOI：
10.1016/b978-0-12-385114-7.00018-0
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发表时间：
2011
影响因子：
--
通讯作者：
Townsend DM
中科院分区：
文献类型：
--
作者：
Uys JD;Xiong Y;Townsend DM
氧化和亚硝化应激导致活性氧和氮物质（ROS/RNS）的积累，其通过半胱氨酸残基上的翻译后修饰（包括S-亚硝基化（P-SNO）和S-谷胱甘肽化（P-SSG））触发氧化还原介导的信号级联。蛋白质二硫键异构酶（PDI）是内质网中最丰富的分子伴侣，通过氧化还原酶活性促进蛋白质折叠。长时间或急性亚硝化应激通过形成PDI-SNO和PDI-SSG减弱PDI的活性。功能含义是，一段时间内活性降低导致错误折叠或未折叠蛋白质的积累和未折叠蛋白质反应的激活。PDI和下游信号传导事件的氧化还原调节为细胞存活途径的功能决定提供了整合点。在此，我们描述的方法，以全球范围内确定S-谷胱甘肽化的ROS/RNS的目标，验证和识别特定的半胱氨酸目标和表征的结构和功能的后果。
Oxidative and nitrosative stress result in the accumulation of reactive oxygen and nitrogen species (ROS/RNS) which trigger redox-mediated signaling cascades through posttranslational modifications on cysteine residues, including S-nitrosylation (P-SNO) and S-glutathionylation (P-SSG). Protein disulfide isomerase (PDI) is the most abundant chaperone in the endoplasmic reticulum and facilitates protein folding via oxidoreductase activity. Prolonged or acute nitrosative stress blunts the activity of PDI through the formation of PDI–SNO and PDI–SSG. The functional implication is that reduced activity for the period of time leads to an accumulation of misfolded or unfolded proteins and activation of the unfolded protein response. Redox regulation of PDI and downstream signaling events provides an integration point for the functional determination of cell survival pathways. Herein, we describe the methodologies to globally identify S-glutathionylated targets of ROS/RNS; validate and identify the specific cysteine targets and characterize the structural and functional consequences.