title: Effects of hypoxia-inducible factor-1α chemical stabilizer, CoCl(2) and hypoxia on gene expression of CYP3As in human fetal liver cells.
abstract: Distinctive response patterns of CYP3A4 and CYP3A7 to cobalt chloride (CoCl(2)) in human fetal liver (HFL) cells were observed and compared with those under hypoxic conditions. The expression levels of CYP3A4 and CYP3A7 mRNAs were decreased by CoCl(2) and hypoxia, although significance could not be determined in HFL cells cultured under 3% O(2). The hypoxia-inducible factor-1α (HIF-1α) protein content in HFL cells was significantly increased by CoCl(2) and 3% O(2). Transcriptional activities of CYP3A4 and CYP3A7 were not altered by 3% O(2) when reporter plasmids containing the promoter region ranging up to about 10 kb and 12 kb upstream, respectively, were transfected into HFL cells, although the activity was significantly suppressed by CoCl(2). These results suggested that the mechanisms controlling CYP3A gene expression of HIF-1α chemical stabilizer in fetal hepatocytes might be different from those in adult hepatocytes, and that HIF-1α is not directly involved in regulation of CYP3A4 or CYP3A7 expression.
authors.affiliation: Department of Molecular Pharmacology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.forename: Tamihide
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Akiko
authors.initials: A
authors.lastname: Aonuma
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nagata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohmori
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D055550:Protein Stability; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C018021:cobaltous chloride