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

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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.