title: Feedback regulation of beta,beta-carotene 15,15'-monooxygenase by retinoic acid in rats and chickens.
abstract: beta,beta-Carotene 15,15'-monooxygenase (formerly termed beta,beta-carotene 15,15'-dioxygenase, EC 1.13.11.21) catalyzes the conversion of provitamin A carotenoids to retinal in vertebrate tissues. In the present study, we investigated whether preformed vitamin A or beta-carotene and its direct metabolites can regulate the enzyme activity in vivo. We found dose-dependent decreases in intestinal beta,beta-carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to -79%), beta-carotene (up to -79%), apo-8'-carotenal (up to -56%), all-trans retinoic acid (up to -88%), and 9-cis retinoic acid (up to -67%). Liver beta,beta-carotene 15,15'-monooxygenase (betaCMOOX) activity was not affected. Apo-12'carotenal and the retinoic acid receptor (RAR) alpha antagonist Ro 41-5253 significantly increased the intestinal enzyme activity by 55 and 94%, respectively. When beta-carotene was administered to rats pretreated with the two cytochrome P(450) (CYP) inducers, pentobarbital and naphthoflavone, the intestinal betaCMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal betaCMOOX. Our data suggest that retinoids and carotenoids might regulate betaCMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family.
authors.affiliation: Roche Vitamins, Human Nutrition and Health, Carotenoid Group, CH-4070 Basel, Switzerland.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Bachmann
authors.forename: Andrew
authors.initials: A
authors.lastname: Desbarats
authors.forename: Peter
authors.initials: P
authors.lastname: Pattison
authors.forename: Megan
authors.initials: M
authors.lastname: Sedgewick
authors.forename: Georges
authors.initials: G
authors.lastname: Riss
authors.forename: Adrian
authors.initials: A
authors.lastname: Wyss
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cardinault
authors.forename: Christelle
authors.initials: C
authors.lastname: Duszka
authors.forename: Regina
authors.initials: R
authors.lastname: Goralczyk
authors.forename: Pascal
authors.initials: P
authors.lastname: Grolier
mesh_terms: D000818:Animals; D001483:Base Sequence; D002645:Chickens; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D017931:DNA Primers; D004790:Enzyme Induction; D005246:Feedback; D005260:Female; D007700:Kinetics; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology; D050559:beta-Carotene 15,15'-Monooxygenase
chemical_list: C493357:Bco1 protein, rat; D017931:DNA Primers; D019207:beta Carotene; D014801:Vitamin A; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D050559:beta-Carotene 15,15'-Monooxygenase