CYP3A7 protein expression is high in a fraction of adult human livers and partially associated with the CYP3A7*1C allele.
Previously, cytochrome P450 3A7 (CYP3A7), which constitutes the major CYP enzyme in fetal livers, has been considered a fetus-specific enzyme. However, CYP3A7 mRNA has recently been shown to be expressed at significant levels in a subset of adult human livers, several of which carry the CYP3A7*1C allele that contains the proximal PXR/CAR element of CYP3A4. The objective of this study was to investigate CYP3A7 expression at the protein level by developing a CYP3A7-specific antibody to allow its quantification. Based on results from 59 adult human liver samples, we found significant CYP3A7 protein expression in approximately one in 10 adult livers amounting for 24-90 pmol/mg microsomal protein, thereby contributing 9-36% to total CYP3A levels in these livers. CYP3A7 protein was detected in five of seven livers carrying the CYP3A7*1C allele (two of which only had trace amounts), whereas an additional three livers expressing CYP3A7 were apparently homozygous for CYP3A7*1. The mean protein expression level of CYP3A7 was 42 pmol/mg within the group of livers expressing CYP3A7 and 4 pmol/mg in all liver samples. CYP3A7 expression was thus higher than that of the polymorphically expressed CYP3A5 in adult human livers, based on a comparison with a previous study using our CYP3A5 peptide-specific antibody. The relatively high level of CYP3A7 protein expression detected in a subset of adult livers may be relevant with respect to the metabolism of exogenous and endogenous substrates, such as retinoic acid and dehydroepiandrosterone.
Sim
Sarah C
SC
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Sarah.Sim@imm.ki.se
Edwards
Robert J
RJ
Boobis
Alan R
AR
Ingelman-Sundberg
Magnus
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000235:genetics*; D015153:Blotting, Western; D051544:Cytochrome P-450 CYP3A; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014212:Tretinoin / Q000378:metabolism
D000276:Adjuvants, Immunologic; D010455:Peptides; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D014212:Tretinoin; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A