Regulation of CYP1A2 by histone deacetylase inhibitors in mouse hepatocytes.
Cytochrome P450 1A2 (CYP1A2) is constitutively expressed in the mouse liver, but the constitutive expression progressively declines to an undetectable level in isolated hepatocytes. In this study, CYP1A2 was induced in hepatocytes exposed to the histone deacetylase inhibitors trichostatin A (TSA) and sodium butyrate (SB), but only well after constitutive CYP1A2 expression was silenced. However, cotreatment with the arylhydrocarbon receptor (AhR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and either TSA or SB reduced the induction of CYP1A2 with the same time course as TSA or SB increased its induction. These results suggest that histone modification is involved in CYP1A2 regulation in hepatocytes through pathways that are independent of AhR.
Jin
Bohwan
B
College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
Ryu
Doug-Young
DY
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D022781:Hepatocytes / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity
D002087:Butyrates; D004785:Environmental Pollutants; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000072317:Polychlorinated Dibenzodioxins; C012589:trichostatin A; D019388:Cytochrome P-450 CYP1A2; D006655:Histone Deacetylases