Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear receptors CAR and PXR play a key role in cytochrome P450 gene induction by xenobiotics. Human cytochrome P450 3A7 (CYP3A7) is expressed from early in gestation until the perinatal period, when there is a switch in expression to CYP3A4. Here we demonstrate that a PXR and CAR responsive enhancer is located approximately 8 kb upstream of the proximal CYP3A7 promoter. This distal xenobiotic responsive enhancer module (XREM) is conserved with the XREM of CYP3A4. Interestingly, not only the XREM, but also the entire promoters exhibit 90% sequence identity up to -8.8 kb, indicating a close evolutionary distance. We propose that the promoters have coevolved to functionally conserve P450 gene induction in response to xenobiotics through CAR and PXR. Thus, nuclear receptors for xenobiotics may not only play a role to provide a survival advantage during adulthood, but also to protect the embryo against endogenous and exogenous toxins.
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PMID:Functionally conserved xenobiotic responsive enhancer in cytochrome P450 3A7. 1116 90

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.
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PMID:CYP3A7 protein expression is high in a fraction of adult human livers and partially associated with the CYP3A7*1C allele. 1604 Dec 41