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Astroglial CYP1B1 up-regulation in inflammatory/oxidative toxic conditions: IL-1beta effect and protection by N-acetylcysteine.
- Source :
-
Toxicology letters [Toxicol Lett] 2003 Mar 03; Vol. 138 (3), pp. 243-51. - Publication Year :
- 2003
-
Abstract
- 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.<br /> (Copyright 2002 Elsevier Science Ireland Ltd.)
- Subjects :
- Aryl Hydrocarbon Hydroxylases genetics
Aryl Hydrocarbon Hydroxylases immunology
Astrocytes drug effects
Astrocytes immunology
Astrocytoma
Cytochrome P-450 CYP1B1
Cytochrome P-450 CYP2D6 genetics
Cytochrome P-450 CYP2D6 immunology
Cytochrome P-450 CYP2D6 metabolism
Drug Interactions
Gene Expression Regulation, Enzymologic drug effects
Gene Expression Regulation, Enzymologic immunology
Humans
Interleukin-1 antagonists & inhibitors
Isoenzymes genetics
Isoenzymes immunology
Isoenzymes metabolism
Microsomes metabolism
Oxidative Stress drug effects
RNA, Messenger biosynthesis
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Up-Regulation immunology
Acetylcysteine pharmacology
Aryl Hydrocarbon Hydroxylases metabolism
Astrocytes enzymology
Interleukin-1 toxicity
Oxidative Stress immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0378-4274
- Volume :
- 138
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 12565201
- Full Text :
- https://doi.org/10.1016/s0378-4274(02)00417-4