title: Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes.
abstract: The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH:cytochrome P450 reductase and NAD(P)H:quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UGTs as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induced a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects were significantly prevented by the presence of melatonin, suggesting its direct antioxidant action on reactive oxygen species, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Results show that both catalytic properties of UGTs and the expression of UGT1A6, UGT1A7, NQO1 and NADPH:cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro-oxidative environment. In conclusion, an experimental increase in oxidative cellular status could have both immediate and long term consequences on detoxification enzymatic system activity and expression.
authors: Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. danielagrdnr@yahoo.com
authors: Daniela
authors: D
authors: Gradinaru
authors: Anne-Laure
authors: AL
authors: Minn
authors: Yves
authors: Y
authors: Artur
authors: Alain
authors: A
authors: Minn
authors: Jean-Marie
authors: JM
authors: Heydel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002384:Catalysis; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009284:Naphthols / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation; D011726:Pyridinium Compounds / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D000975:Antioxidants; D020719:Glucuronides; D009284:Naphthols; D016877:Oxidants; D011726:Pyridinium Compounds; D011809:Quinones; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C029350:1-naphthol; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7; D008550:Melatonin