The eccentric cleavage product of β-carotene, β-apo-13-carotenone, functions as an antagonist of RXRα

被引：57
作者：
Eroglu, Abdulkerim [1 ,2 ]
Hruszkewycz, Damian P. [3 ]
Curley, Robert W., Jr. [2 ,3 ]
Harrison, Earl H. [1 ,2 ]
机构：
[1] Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA
[2] Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA
[3] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA
来源：
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2010年 / 504卷 / 01期
关键词：
beta-Apocarotenoids; Retinoids; Retinoid receptors; Carotenoids; RETINOID-X-RECEPTOR; NUCLEAR RECEPTOR; THYROID-HORMONE; VITAMIN-A; ACID; BINDING; IDENTIFICATION; LIGAND; 15,15'-DIOXYGENASE; ABSORPTION;
D O I：
10.1016/j.abb.2010.07.025
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In this study, we investigated the effects of eccentric cleavage products of beta-carotene, i.e. beta-apocarotenoids (BACs), on retinoid X receptor alpha (RXR alpha) signaling. Transactivation assays were performed to test whether BACs activate or antagonize RXR alpha. Reporter gene constructs (RXRE-Luc, pRL-tk) and RXR alpha were transfected into Cos-1 cells and used to perform these assays. None of the BACs tested activated RXR alpha. Among the compounds tested, beta-apo-13-carotenone was found to antagonize the activation of RXR alpha by 9-cis-retinoic acid and was effective at concentrations as low as 1 nM. Molecular modeling studies revealed that beta-apo-13-carotenone makes molecular interactions like an antagonist of RXR alpha. The results suggest a possible function of BACs on RXR alpha signaling. (C) 2010 Elsevier Inc. All rights reserved.
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收藏
页码：11 / 16
页数：6
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