title: Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells.
abstract: Mutation in DJ-1 gene is the cause of autosomal recessive Parkinson's disease, however, its physiological function remains unclear. The isoelectric point of DJ-1 shows an acidic shift after cells are treated with hydrogen peroxide. This suggests that DJ-1 is modified in response to oxidative stress. Here we report the structural characterization of an acidic isoform of DJ-1 using a proteomic approach with nanospray interface liquid chromatography-electrospray ionization/linear ion trap mass spectrometer. When human umbilical vein endothelial cells were exposed to hydrogen peroxide, all three cysteines in DJ-1 were oxidized to cysteine sulphonic acid. Although a small part of the Cys-46 and Cys-53 were oxidized, Cys-106 was oxidized completely at any hydrogen peroxide concentration used here. These results suggest that Cys-106 is the most sensitive among three cysteine residues to oxidative stress, and that DJ-1 function is regulated, in terms of the intracellular redox state, by oxidation of Cys-106.
authors.affiliation: Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Osaka 563-8577, Japan. t.kinumi@aist.go.jp
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kinumi
authors.forename: Junko
authors.initials: J
authors.lastname: Kimata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taira
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D003545:Cysteine / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D006861:Hydrogen Peroxide; D003545:Cysteine