Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells.
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Malaplate-Armand C, Ferrari L, Masson C, Visvikis-Siest S, Lambert H, Batt AM
Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells.
Toxicol Lett. 2005 Dec 15;159(3):203-11. doi: 10.1016/j.toxlet.2005.04.005. Epub 2005 Sep 26.
- PubMed ID
- 16188404 [ View in PubMed]
- Abstract
Psychostimulant drugs abuse is associated with an increased risk of stroke. Cytochromes P450 (CYP), especially the astrocytic members of the CYP2C subfamily may play an important role in the modulation of cerebrovascular functions, by generating vasodilatator metabolites from arachidonic acid (AA). Our study examined the regulation of CYP2C genes in response to cocaine or amphetamine in the human astrocyte-like U373 MG cells, using reverse transcription-polymerase chain reaction (RT-PCR) and western-blot analysis. A treatment for 48h with increasing concentrations of cocaine caused a significant down-regulation of CYP2C8 and CYP2C9 genes and decreased the protein level. These effects were not observed with amphetamine. One mechanism of the CYP2C mRNA regulation implicates various specific receptors including glucocorticoid receptor (GR) and constitutive androstane receptor (CAR). Effects of cocaine on CYP2C were accompanied by a decrease in the GR and CAR gene expression suggesting that these nuclear receptors could be involved in the CYP2C repression by cocaine in the U373 MG cell line. These findings represent a possible molecular mechanism involved in the cerebrovascular risk associated with cocaine abuse.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Cocaine Cytochrome P450 2C8 Protein Humans UnknownDownregulatorDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Cocaine Approved Illicit CYP2C8 1558 downregulated Cocaine results in decreased expression of CYP2C8 mRNA 10q23.33 Cocaine Approved Illicit CYP2C9 1559 downregulated Cocaine results in decreased expression of CYP2C9 mRNA 10q23.33 Cocaine Approved Illicit NR1I3 9970 downregulated Cocaine results in decreased expression of NR1I3 mRNA 1q23.3 Cocaine Approved Illicit NR3C1 2908 downregulated Cocaine results in decreased expression of NR3C1 mRNA 5q31.3