Astroglial CYP1B1 up-regulation in inflammatory/oxidative toxic conditions: IL-1β effect and protection by N-acetylcysteine

• Published in: Toxicology letters Vol. 138; no. 3; pp. 243 - 251
• Main Authors: Malaplate-Armand, C., Ferrari, L., Masson, C., Siest, G., Batt, A.M.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 03.03.2003; Amsterdam Elsevier Science
• Subjects: Astrocytoma; Biological and medical sciences; CYP1B1; CYP2D6; Cytochrome P450; General aspects. Methods; Interleukin-1β; Medical sciences; Toxicology; Cytochrome P450; Interleukin-1β; TNFα, tumor necrosis factor α; NAC, N-acetylcysteine; IL-1β, interleukin-1β; AhR, aryl hydrocarbon receptor; CNS, central nervous system; CYP2D6; β2M, β2-microglobuline; IL-6, interleukin-6; CYP1B1; PCR, polymerase chain reaction; RT, reverse transcriptase; P450, cytochrome P450; Astrocytoma; Human; Oxidative stress; Nervous system diseases; Isozyme; Toxicity; Cytokine; Glioblastoma; Acetylcysteine; Interleukin 1β; Inflammation; Antioxidant; Gene expression; In vitro; Dose activity relation; Sulfur containing aminoacid; Prevention; Cell line; Mechanism of action; Tumor cell
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(02)00417-4

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-1β (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.