The Regenerative System for Proteins inactivated by Oxidative Stress in Cardiovascular System

心血管系统中氧化应激失活的蛋白质再生系统

• 批准号: 06670755
• 负责人: IKEDA Masaharu
• 金额: $ 1.34万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670755/
• 关键词: Thioredoxin; Thioredoxin Reductase; Glutaredoxin; Oxidative Stress; Regeneration; Vascular Endothelial Cells; Heart

Protein thiol/disulfide exchanging enzymes such as thioredoxin, thioredocin reductase, glutaredoxin and protein disulfide isomerase were studied as a regenerative (or repair) system for proteins inactivated by oxidative stress using cultured endothelial cells and whole hearts.The results obtained in this study were ;1. Thioredoxin, thioredoxin reductase, glutaredoxin and protein disulfide isomerase were involved in the regeneration reaction of proteins inactivated by oxidative stress in endothelial cells.2. Thioredoxin and glutaredoxin exhibited the different substrate specificity in the regeneration reaction of the oxidatively-damaged proteins.3. The protein levels of thioredoxin and protein disulfide isomerase in vascular endothelial cells and whole hearts were increased by exposure to oxidative stress.4. Human glutaredoxin cDNA was cloned.5. Thioredoxin and thioredoxin reductase were found to be localized in both cytosol and mitochondrial fractions of bovine heart. These enzymes were isolated from each compartment.6. Thioredoxin/thioredoxin reductase system was found to exert a protective effect on the nitric oxidemediated inhibition of mitochondrial respiratory activity.These findings indicated that these protein thiol/disulfide exchanging enzymes, especially thioredoxin/thioredoxin reductase system playd an important role in the cellular antioxidant defense mechanism by functioning as an endogenous regeneration system for oxidatively-damaged proteins.

使用培养的内皮细胞和整个心脏，研究了蛋白质硫醇/二硫键交换酶（例如硫氧还蛋白、硫氧还蛋白还原酶、谷氧还蛋白和蛋白质二硫键异构酶）作为因氧化应激而失活的蛋白质的再生（或修复）系统。 1.硫氧还蛋白、硫氧还蛋白还原酶、谷氧还蛋白和蛋白质二硫键异构酶参与内皮细胞氧化应激失活蛋白质的再生反应。 2．硫氧还蛋白和谷氧还蛋白在氧化损伤蛋白的再生反应中表现出不同的底物特异性。 3．氧化应激使血管内皮细胞和全心脏硫氧还蛋白和蛋白二硫键异构酶蛋白水平升高。 4．克隆了人谷氧还蛋白cDNA。 5．发现硫氧还蛋白和硫氧还蛋白还原酶位于牛心脏的细胞质和线粒体部分中。这些酶是从每个隔室中分离出来的。6．硫氧还蛋白/硫氧还蛋白还原酶系统被发现对一氧化氮介导的线粒体呼吸活性抑制发挥保护作用。这些发现表明这些蛋白质硫醇/二硫键交换酶，特别是硫氧还蛋白/硫氧还蛋白还原酶系统在细胞抗氧化防御机制中发挥着重要作用。作为氧化损伤蛋白质的内源性再生系统。

项目成果

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