Feedback Regulation of β,β-Carotene 15,15′-Monooxygenase by Retinoic Acid in Rats and Chickens

• Published in: The Journal of nutrition Vol. 132; no. 12; pp. 3616 - 3622
• Main Authors: Bachmann, Heinrich, Desbarats, Andrew, Pattison, Peter, Sedgewick, Megan, Riss, Georges, Wyss, Adrian, Goralczyk, Regina, Cardinault, Nicolas, Duszka, Christelle, Grolier, Pascal
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.12.2002; American Society for Nutritional Sciences
• Subjects: Animals; antagonists; Base Sequence; beta Carotene - pharmacology; beta-carotene; beta-Carotene 15,15'-Monooxygenase; Biological and medical sciences; Chickens; cytochrome P-450; Cytochrome P-450 Enzyme System - biosynthesis; DNA Primers; enzyme activity; Enzyme Induction; Feedback; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Kinetics; liver; metabolites; oral administration; Oxygenases - metabolism; pentobarbital; RARα; Rats; retinoic acid; retinoic acid regulation; retinyl acetate; transcription (genetics); Tretinoin - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; vitamin A; Vitamin A - pharmacology; β-carotene cleavage; βCMOOX; SSC; β-carotene cleavage; 13RA; RARα; 9RA; RXR; RA; chickens; LDH; retinoic acid regulation; rats; CYP; GSH; β-Carotene 15,15'-dioxygenase; Rat; Retinoid; Feedback regulation; Supplemented diet; Enzymatic activity; Aves; Enzyme; Rodentia; Metabolism; RXRα retinoid receptor; Feeding; Micronutrient; Vertebrata; Mammalia; Animal; Chicken; Oxidoreductases; Betacarotene; Carotenoid; Retinoic acid
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/132.12.3616

β,β-Carotene 15,15′-monooxygenase (formerly termed β,β-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 β-carotene and its direct metabolites can regulate the enzyme activity in vivo. We found dose-dependent decreases in intestinal β,β-carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to −79%), β-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 β,β-carotene 15,15′-monooxygenase (βCMOOX) activity was not affected. Apo-12′carotenal and the retinoic acid receptor (RAR) α antagonist Ro 41-5253 significantly increased the intestinal enzyme activity by 55 and 94%, respectively. When β-carotene was administered to rats pretreated with the two cytochrome P450 (CYP) inducers, pentobarbital and naphthoflavone, the intestinal βCMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal βCMOOX. Our data suggest that retinoids and carotenoids might regulate βCMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family.