The fetal specific gene CYP3A7 is inducible by rifampicin in adult human hepatocytes in primary culture.
We investigated by RNase protection the differential expression of CYP3A4 and CYP3A7 mRNAs in fetal and adult human livers and in adult hepatocytes in primary culture. Our results show that CYP3A7 is expressed in the liver of 8 of 9 adult Caucasians examined, at an average level of 1.7% of the level found in a fetal liver. CYP3A4 mRNA appeared to be expressed in this fetal liver. In adult hepatocytes in primary culture, the constitutive level of CYP3A4 mRNA was low but detectable after 96 hours in untreated cells, but CYP3A7 mRNA remained undetectable. However, when the cells were treated for 48 hours with 25 microM rifampicin, both CYP3A4 and CYP3A7 mRNAs were strongly induced in the 3 and in 2 of 3 cultures examined, respectively. Using an isoelectric focusing immunoblotting the two proteins were resolved. Protein CYP3A4 was detectable in induced cells but CYP3A7 was not. These results show for the first time that CYP3A7 and CYP3A4 mRNAs, but not the proteins, are co-inducible by rifampicin in adult human hepatocytes in culture.
Greuet
J
J
INSERM U-128, CNRS, Montpellier, France.
Pichard
L
L
Bonfils
C
C
Domergue
J
J
Maurel
P
P
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*
D017931:DNA Primers; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A; D012293:Rifampin