Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1.
Pyrroloquinoline quinone (PQQ) has been shown to play a role as an anti-oxidant in neuronal cells and prevent neuronal cell death in a rodent stroke model. DJ-1, a causative gene product for a familial form of Parkinson's disease, plays a role in anti-oxidative stress function by self-oxidation of DJ-1. In this study, the expression level and oxidation status of DJ-1 were examined in SHSY-5Y cells and primary cultured neurons treated with 6-hydroxydopamine (6-OHDA) or H(2)O(2) in the presence or absence of PQQ. The pI shift of DJ-1 to an acidic point, which was observed in SHSY-5Y cells treated with 6-OHDA, was inhibited by PQQ. TOF-MS analyses showed that while the level of a reduced form of DJ-1, one of the active forms of DJ-1, was decreased in SHSY-5Y cells treated with 6-OHDA or H(2)O(2), PQQ increased the level of the reduced form of DJ-1. These results suggest that PQQ prevents oxidative stress-induced changes in oxidative status of DJ-1. Therefore, the neuroprotective effects of PQQ on oxidative stress-induced neuronal death may be at least in part involved in increased level of an active form of DJ-1.
Nunome
Kana
K
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Miyazaki
Shin
S
Nakano
Masahiko
M
Iguchi-Ariga
Sanae
S
Ariga
Hiroyoshi
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D011247:Pregnancy; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D008869:Microtubule-Associated Proteins; D016877:Oxidants; D011758:Pyrroles; D011804:Quinolines; D013778:Tetrazolium Salts; D013844:Thiazoles; C410406:pyrroloquinoline; D014810:Vitamin E; D016627:Oxidopamine; D006861:Hydrogen Peroxide; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; C022616:thiazolyl blue; D001205:Ascorbic Acid