title: Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.
abstract: The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.
authors.affiliation: a Department of Applied Molecular Biosciences , Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya , Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hoshinaga
authors.forename: Natsuko
authors.initials: N
authors.lastname: Miura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Shigeoka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Murai
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Horio
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism*; D004198:Disease Susceptibility; D003576:Electron Transport Complex IV / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012614:Scurvy / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1; C025619:steroid 16-beta-hydroxylase; D051547:Heme Oxygenase-1; D003576:Electron Transport Complex IV; D010634:Phenobarbital
keywords: CYP2B1/2B2; ODS rat; ascorbic acid; cytochrome P-450; heme oxygenase-1