title: Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level.
abstract: Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.
authors.affiliation: The William Harvey Research Institute, St. Bartholomew's Medical College, London, UK. okhatsen@uci.edu
authors.forename: O G
authors.initials: OG
authors.lastname: Khatsenko
authors.forename: A R
authors.initials: AR
authors.lastname: Boobis
authors.forename: S S
authors.initials: SS
authors.lastname: Gross
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013250:Steroid Hydroxylases / Q000187:drug effects / Q000235:genetics*
chemical_list: D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1; C025619:steroid 16-beta-hydroxylase