Astroglial CYP1B1 up-regulation in inflammatory/oxidative toxic conditions: IL-1beta effect and protection by N-acetylcysteine.
The present work aims to determine the relevance of an astrocytoma cell line U373 MG, for assessing the role of some astroglial cytochrome P450 in neurotoxicity and neuroprotection. CYP1B1, CYP2C8, CYP2C9, CYP2D6, CYP2J2, CYP2E1 and CYP4A11 mRNA were detected by reverse transcriptase-polymerase chain reaction in control U373 MG cell cultures. Among them we focused on CYP1B1 expression. After 48 h treatment with a range of concentrations of interleukin-1beta (1, 5, 10 ng/ml) used to simulate stress conditions, CYP1B1 mRNA expression was enhanced in a dose-dependent way. This increased expression was followed 24 h later by an increase in protein level, determined by Western-blot. N-acetylcysteine (NAC) partially inhibited this effect both on the mRNA and protein levels. As CYP1B1 activates procarcinogenic compounds to reactive metabolites, an increase in this P450 isoform will participate to toxic consequences of an inflammatory/oxidative stress. NAC will prevent this deleterious effect.
Malaplate-Armand
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Centre du Médicament, Inserm U525, Faculté de Pharmacie, Université Henri Poincaré Nancy I, 30 rue Lionnois, 54000 Nancy, France.
Ferrari
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Masson
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Siest
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Batt
A M
AM
D000111:Acetylcysteine / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D001254:Astrocytoma; D065633:Cytochrome P-450 CYP1B1; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D019389:Cytochrome P-450 CYP2D6; D000111:Acetylcysteine