Abstract
We examined the effects of model activators of mitogen-activated protein kinases (MAPKs) on basal and rifampicin-, phenobarbital- and dioxin-inducible expression of phase I and phase II biotransformation enzymes in primary human hepatocytes. Cells were treated for 24 h with sorbitol (SOR), anisomycin (ANI) and epidermal growth factor (EGF) in the presence or absence of inducers. The levels of CYP1A1, CYP1A2, CYP2B6, CYP3A4, UGT1A1, UGT2B17, SULT1A1, SULT2A1, SULT1B2, GSTA1, GSTA2 mRNAs were determined. SOR and EGF inhibited the expression of the tested genes, while ANI had no effect. We conclude that MAPKs play important role in the transcriptional regulation of drug-metabolizing enzymes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anisomycin / pharmacology
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Aryl Hydrocarbon Hydroxylases / metabolism
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Dioxins / pharmacology
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Enzyme Activation / drug effects
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Enzyme Activators / pharmacology
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Epidermal Growth Factor / metabolism
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Glucuronosyltransferase / metabolism
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Glutathione Transferase / metabolism
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Hepatocytes / drug effects
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Hepatocytes / enzymology*
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Hepatocytes / metabolism
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Humans
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Phenobarbital / pharmacology
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RNA, Messenger / metabolism
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Rifampin / pharmacology
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Sorbitol / pharmacology
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Sulfotransferases / metabolism
Substances
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Dioxins
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Enzyme Activators
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RNA, Messenger
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Sorbitol
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Epidermal Growth Factor
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Anisomycin
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Aryl Hydrocarbon Hydroxylases
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Glucuronosyltransferase
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Glutathione Transferase
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Extracellular Signal-Regulated MAP Kinases
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Sulfotransferases
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Rifampin
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Phenobarbital