Oxidation of proteinaceous cysteine residues by dopamine-derived H2O2 in PC12 cells.
Cellular metabolism of dopamine (DA) generates H2O2, which is further reduced to hydroxyl radicals in the presence of iron. Cellular damage inflicted by DA-derived hydroxyl radicals is thought to contribute to Parkinson's disease. We have previously developed procedures for detecting proteins that contain H2O2-sensitive cysteine (or selenocysteine) residues. Using these procedures, we identified ERP72 and ERP60, two members of the protein disulfide isomerase family, creatine kinase, glyceraldehyde-3-phosphate dehydrogenase, phospholipase C-gamma1, and thioredoxin reductase as the targets of DA-derived H2O2. Experiments with purified enzymes identified the essential Cys residues of creatine kinase and glyceraldehyde-3-phosphate dehydrogenase, that are specifically oxidized by H2O2. Although the identified proteins represent only a fraction of the targets of DA-derived H2O2, functional impairment of these proteins has previously been associated with cell death. The oxidation of proteins that contain reactive Cys residues by DA-derived H2O2 is therefore proposed both to be largely responsible for DA-induced apoptosis in neuronal cells and to play an important role in the pathogenesis of Parkinson's disease.
Kim
Jae-Ryong
JR
Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA.
Kwon
Ki-Sun
KS
Yoon
Hae Won
HW
Lee
Seung-Rock
SR
Rhee
Sue Goo
SG
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002374:Catalase / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010300:Parkinson Disease / Q000209:etiology; D051966:Phospholipase C gamma; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D006861:Hydrogen Peroxide; D002374:Catalase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D013880:Thioredoxin-Disulfide Reductase; D003402:Creatine Kinase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D019704:Protein Disulfide-Isomerases; D003545:Cysteine; D004298:Dopamine; D000111:Acetylcysteine