Open AccessHeme may not be a positive regulator of cytochrome‐ P 450 gene expression
Author(s) -
SRIVASTAVA Gopesh,
BAWDEN Michael J.,
HANSEN Antony J.,
MAY Brian K.
Publication year - 1989
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1989.tb14499.x
Subject(s) - heme , cytochrome p450 , cytochrome , messenger rna , biochemistry , atp synthase , chemistry , biology , gene expression , transcription (linguistics) , microbiology and biotechnology , enzyme , gene , linguistics , philosophy
It has been proposed that transcription of cytochrome‐ P 450 genes is positively regulated by heme, the prosthetic group of cytochrome‐ P 450 proteins. We have investigated this proposal in rats treated with succinylacetone, a known specific inhibitor of the heme biosynthetic pathway. While 2‐allyl‐2‐isopropylacetamide, phenobarbitone, dexamethasone, β‐naphthoflavone and clofibrate induced specific cytochrome‐ P 450‐mRNA species in rat liver, the levels of these induced mRNAs were not affected by succinylacetone administration. Synthesis of the first enzyme of the heme biosynthetic pathway, 5‐aminolevulinate synthase, is known to be regulated by the end‐product heme, with heme inhibiting 5‐aminolevulinate‐synthase‐gene transcription. Hepatic 5‐aminolevulinate‐synthase mRNA was induced by drugs and the level increased further by succinylacetone. Furthermore, treatment of rats with succinylacetone alone resulted in elevated levels of 5‐aminolevulinate‐synthase mRNA but did not affect cytochrome‐ P 450‐mRNA levels. The results show that while lowered heme levels lead to an increase in 5‐aminolevulinate‐synthase‐mRNA synthesis there is no effect on cytochrome‐ P 450‐mRNA levels, implying that heme is not required for the cytochrome‐ P 450‐gene transcription.