Heme is a positive regulator of cytochrome P-450 gene transcription.
Inhibitors of heme biosynthesis such as CoCl2, 3-amino-1,2,4-triazole, and thioacetamide block the 3-methylcholanthrene-mediated induction of cytochrome P-450 (c + d) messenger RNAs and their transcription in rat liver. This effect is specific, since the messenger RNA levels for albumin and glutathione transferase (Ya + Yc) and their transcription are not significantly influenced under conditions of heme depletion. Exogenous administration of heme at very low doses (50 micrograms/100 g body wt) is able to completely counteract the effects of the heme biosynthetic inhibitors on cytochrome P-450 (c + d) messenger RNA levels and their transcription. This constitutes a direct proof for the role of heme as a positive regulator of cytochrome P-450 gene transcription.
Bhat
G J
GJ
Department of Biochemistry, Indian Institute of Science, Bangalore.
Padmanaban
G
G
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D003035:Cobalt / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D006418:Heme / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013853:Thioacetamide / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D004274:DNA, Recombinant; D012333:RNA, Messenger; D013853:Thioacetamide; D003035:Cobalt; D006418:Heme; D008748:Methylcholanthrene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C018021:cobaltous chloride; D000640:Amitrole