Transgenic yeast expressing human cytochrome P450s can serve as a tool in studies of the mechanisms of their induction by various effectors.
Transgenic Saccharomyces cerevisiae yeast strains were constructed which express CYP2D6 and CYP3A4 genes under control of an artificial promoter. When added to the growth medium, sparteine, a substrate for CYP2D6, was shown to increase the content of this cytochrome P450 isoform in yeast cells. No such increase was observed when a proteinase-deficient yeast mutant was used as a parent strain. Nifedipine, a substrate for CYP3A4, failed to affect the level of CYP3A4 expression even in wild yeast cells. These results suggest that expression of CYP2D6 in human liver can at least partially be controlled post-transcriptionally by its inductors while for CYP3A4 such a mechanism is hardly possible.
Kovaleva
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A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University, Russia.
Krynetskii
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Luzikov
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D003001:Cloning, Molecular; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics*; D009543:Nifedipine / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013034:Sparteine / Q000494:pharmacology
D013034:Sparteine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009543:Nifedipine