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.

引用

页码：11 / 16

页数：6

共 52 条

[1]

ALLEGRETTO EA, 1993, J BIOL CHEM, V268, P26625

[2] DESIGN AND SYNTHESIS OF POTENT RETINOID-X RECEPTOR-SELECTIVE LIGANDS THAT INDUCE APOPTOSIS IN LEUKEMIA-CELLS [J].

BOEHM, MF ;

ZHANG, L ;

ZHI, L ;

MCCLURG, MR ;

BERGER, E ;

WAGONER, M ;

MAIS, DE ;

SUTO, CM ;

DAVIES, PJA ;

HEYMAN, RA ;

NADZAN, AM .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (16) :3146-3155

[3] SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NOVEL RETINOID-X RECEPTOR-SELECTIVE RETINOIDS [J].

BOEHM, MF ;

ZHANG, L ;

BADEA, BA ;

WHITE, SK ;

MAIS, DE ;

BERGER, E ;

SUTO, CM ;

GOLDMAN, ME ;

HEYMAN, RA .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (18) :2930-2941

[4] SYNTHESIS OF HIGH SPECIFIC ACTIVITY [H-3] 9-CIS-RETINOIC ACID AND ITS APPLICATION FOR IDENTIFYING RETINOIDS WITH UNUSUAL BINDING-PROPERTIES [J].

BOEHM, MF ;

MCCLURG, MR ;

PATHIRANA, C ;

MANGELSDORF, D ;

WHITE, SK ;

HEBERT, J ;

WINN, D ;

GOLDMAN, ME ;

HEYMAN, RA .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (03) :408-414

[5] MAX3/CCD7 is a carotenoid cleavage dioxygenase required for the synthesis of a novel plant signaling molecule [J].

Booker, J ;

Auldridge, M ;

Wills, S ;

McCarty, D ;

Klee, H ;

Leyser, O .

CURRENT BIOLOGY, 2004, 14 (14) :1232-1238

[6] NEW METHODS FOR OXIDATION OF ALDEHYDES TO CARBOXYLIC ACIDS AND ESTERS [J].

COREY, EJ ;

GILMAN, NW ;

GANEM, BE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1968, 90 (20) :5616-&

[7] Crystal structure of the human RXRα ligand-binding domain bound to its natural ligand:: 9-cis retinoic acid [J].

Egea, PF ;

Mitschler, A ;

Rochel, N ;

Ruff, M ;

Chambon, P ;

Moras, D .

EMBO JOURNAL, 2000, 19 (11) :2592-2601

[8] UNIQUE RESPONSE PATHWAYS ARE ESTABLISHED BY ALLOSTERIC INTERACTIONS AMONG NUCLEAR HORMONE RECEPTORS [J].

FORMAN, BM ;

UMESONO, K ;

CHEN, J ;

EVANS, RM .

CELL, 1995, 81 (04) :541-550

[9] Structural basis for autorepression of retinoid X receptor by tetramer formation and the AF-2 helix [J].

Gampe, RT ;

Montana, VG ;

Lambert, MH ;

Wisely, GB ;

Milburn, MV ;

Xu, HE .

GENES & DEVELOPMENT, 2000, 14 (17) :2229-2241

[10] IDENTIFICATION OF A RECEPTOR FOR THE MORPHOGEN RETINOIC ACID [J].

GIGUERE, V ;

ONG, ES ;

SEGUI, P ;

EVANS, RM .

NATURE, 1987, 330 (6149) :624-629

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