title: Oxidation of DJ-1 induced by 6-hydroxydopamine decreasing intracellular glutathione.
abstract: DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been reported to undergo preferential oxidation of the cysteine residue at position 106 (Cys-106) under oxidative stress; however, details of the molecular mechanisms are not well known. In the present study, mechanisms of DJ-1 oxidation induced by 6-hydroxydopamine (6-OHDA) were investigated by using SH-SY5Y cells. The treatment of these cells with 6-OHDA caused an obvious acidic spot sift of DJ-1 due to its oxidation. However, when catalase, which is an hydrogen peroxide (H(2)O(2))-removing enzyme, was added during the treatment, it failed to prevent the oxidation induced by 6-OHDA, suggesting that electrophilic p-quinone formed from 6-OHDA, but not H(2)O(2), was responsible for the DJ-1 oxidation. Benzoquinone, another electrophilic p-quinone, also induced DJ-1 oxidation. The intracellular glutathione (GSH) levels were significantly decreased by 6-OHDA, irrespective of the presence or absence of catalase. The inhibition of GSH synthesis by buthionine sulfoximine resulted in a decrease in GSH levels and enhancement of DJ-1 oxidation. The pretreatment of cells with N-acetyl-cysteine prevented the loss of intracellular GSH and subsequently DJ-1 oxidation induced by 6-OHDA. Collectively, these results suggest that electrophilic p-quinone formed from 6-OHDA induces DJ-1 oxidation by decreasing intracellular GSH.
authors: Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Tatara, Kyotanabe, Kyoto, Japan.
authors: Akiko
authors: A
authors: Miyama
authors: Yoshiro
authors: Y
authors: Saito
authors: Kazunori
authors: K
authors: Yamanaka
authors: Kojiro
authors: K
authors: Hayashi
authors: Takao
authors: T
authors: Hamakubo
authors: Noriko
authors: N
authors: Noguchi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D016627:Oxidopamine / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016227:Benzoquinones; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D020011:Protective Agents; C004532:quinone; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D002374:Catalase; C105131:PARK7 protein, human; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; D005978:Glutathione; D000111:Acetylcysteine