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© 2002 The American Society for Nutritional Sciences J. Nutr. 132:3616-3622, December 2002


Nutrient-Gene Interactions

Feedback Regulation of ß,ß-Carotene 15,15'-Monooxygenase by Retinoic Acid in Rats and Chickens

Heinrich Bachmann, Andrew Desbarats, Peter Pattison, Megan Sedgewick, Georges Riss, Adrian Wyss1, Nicolas Cardinault*, Christelle Duszka*, Regina Goralczyk and Pascal Grolier*

Roche Vitamins, Human Nutrition and Health, Carotenoid Group, CH-4070 Basel, Switzerland * INRA, Unité des Maladies Métaboliques, Equipe Vitamines, 63009 Clermont-Ferrand, France

1To whom correspondence should be addressed. E-mail: adrian.wyss{at}roche.com.

ß,ß-Carotene 15,15'-monooxygenase (formerly termed ß,ß-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 ß-carotene and its direct metabolites can regulate the enzyme activity in vivo. We found dose-dependent decreases in intestinal ß,ß-carotene monooxygenase activity after oral administration to rats of retinyl acetate (up to -79%), ß-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 ß,ß-carotene 15,15'-monooxygenase (ßCMOOX) 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 ß-carotene was administered to rats pretreated with the two cytochrome P450 (CYP) inducers, pentobarbital and naphthoflavone, the intestinal ßCMOOX activity increased by 39%. In a transcriptional study in chickens, treatment with retinoic acid resulted in low expression of the intestinal ßCMOOX. Our data suggest that retinoids and carotenoids might regulate ßCMOOX expression by a transcriptional feedback mechanism via interaction with members of the RAR family.


KEY WORDS: • ß-carotene cleavage • retinoic acid regulation • RAR{alpha} • rats • chickens




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