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.

Research highlights
► All possible eccentric cleavage products of all-trans β carotene (β-apocarotenoids) were tested as possible activators or inhibitors of RXRα transactivation.
► β-Apocarotenoids did not significantly activate RXRα.
► β-Apo-13-carotenone was a potent antagonist of 9-cis-retinoiic acid activation of RXRα.
► Molecular modeling showed that β-apo-13-carotenone can occupy the ligand-binding site of RXRα.