Pyrroloquinoline Quinone Prevents Oxidative Stress-Induced Neuronal Death Probably through Changes in Oxidative Status of DJ-1

• Published in: Biological & pharmaceutical bulletin 2008/07/01, Vol.31(7), pp.1321-1326
• Main Authors: Nunome, Kana, Miyazaki, Shin, Nakano, Masahiko, Iguchi-Ariga, Sanae, Ariga, Hiroyoshi
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Ascorbic Acid - pharmacology; Blotting, Western; Cell Death - drug effects; Cell Survival - drug effects; DJ-1; Dose-Response Relationship, Drug; Female; Hydrogen Peroxide - antagonists & inhibitors; Hydrogen Peroxide - toxicity; Microtubule-Associated Proteins - drug effects; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neurons - drug effects; neurotoxity; Oxidants - antagonists & inhibitors; Oxidants - toxicity; Oxidation-Reduction; oxidative stress; Oxidative Stress - drug effects; Oxidopamine - antagonists & inhibitors; Oxidopamine - toxicity; Pregnancy; Protein Binding; Protein Deglycase DJ-1; Pyrroles - pharmacology; pyrroloquinoline quinone; Quinolines - pharmacology; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Vitamin E - pharmacology
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.1321

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 H2O2 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 H2O2, 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.