Feedback Regulation of β,β-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.

Lycopene induces retinoic acid receptor transcriptional activation in mice

“…Feedback mechanisms have previously been demonstrated for RA-treatment induced down-regulation of Bco-1 expression in chickens and rats (Bachmann, et al, 2002). In the mouse testis, a strong down-regulation of Bco-1…”

“…It is known that BCO1 and BCO2 are tissue specifically expressed to facilitate the retinoid signaling. It has been previously demonstrated that RA down-regulates the BCO1 mRNA level in chickens and rats (Bachmann, et al, 2002). A study by Zaripheh et al showed that lycopene is the inhibitor of BCO1 as well .…”

Altered Expression of Both β-Carotene 15,15' Monooxygenase and Lecithin:Retinol Acyltransferase in Obese Zucker Rats

“…BCM expression is inversely regulated by retinoic acid in rats with vitamin A deficiency (25). Bachmann and colleagues reported that BCM expression in the chicken intestine is under feedback regulation by retinoic acid and that BCM activity is down-regulated in the rat intestine (27). These studies indicate that retinoic acid may repress BCM gene expression in the principal tissues for retinol metabolism.…”

β-Carotene conversion products and their effects on adipose tissue

“…Approximately, 45% of the western population can be classified as low converter [30,47]. It has been established that conversion efficiency is depending at least in part on the vitamin A status [57], which is explained by the existence of a negative feedback of RA on BCMO1 mRNA expression [3,66]. Besides, many studies have highlighted the huge interindividual variability in conversion efficiency, with a coefficient of variation being as high as 221% [7,12,30,47].…”