Feedback regulation of beta,beta-carotene 15,15'-monooxygenase by retinoic acid in rats and chickens.
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.
Bachmann
Heinrich
H
Roche Vitamins, Human Nutrition and Health, Carotenoid Group, CH-4070 Basel, Switzerland.
Desbarats
Andrew
A
Pattison
Peter
P
Sedgewick
Megan
M
Riss
Georges
G
Wyss
Adrian
A
Cardinault
Nicolas
N
Duszka
Christelle
C
Goralczyk
Regina
R
Grolier
Pascal
P
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
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