The eccentric cleavage product of β-carotene, β-apo-13-carotenone, functions as an antagonist of RXRα.
In this study, we investigated the effects of eccentric cleavage products of β-carotene, i.e. β-apocarotenoids (BACs), on retinoid X receptor alpha (RXRα) signaling. Transactivation assays were performed to test whether BACs activate or antagonize RXRα. Reporter gene constructs (RXRE-Luc, pRL-tk) and RXRα were transfected into Cos-1 cells and used to perform these assays. None of the BACs tested activated RXRα. Among the compounds tested, β-apo-13-carotenone was found to antagonize the activation of RXRα by 9-cis-retinoic acid and was effective at concentrations as low as 1 nM. Molecular modeling studies revealed that β-apo-13-carotenone makes molecular interactions like an antagonist of RXRα. The results suggest a possible function of BACs on RXRα signaling.
Eroglu
Abdulkerim
A
Department of Human Nutrition, The Ohio State University, Columbus, OH 43210, USA.
Hruszkewycz
Damian P
DP
Curley
Robert W
RW
Harrison
Earl H
EH
D000818:Animals; D019556:COS Cells; D002338:Carotenoids / Q000378:metabolism* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051381:Rats; D047490:Retinoid X Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D019207:beta Carotene / Q000378:metabolism*
D008024:Ligands; D047490:Retinoid X Receptor alpha; D019207:beta Carotene; D002338:Carotenoids; D014212:Tretinoin; C071310:beta-apo-13-carotenone