Poster abstracts

Poster number 86 submitted by Kerim Eroglu

Effects of apocarotenoids on activation of retinoic acid receptors (RARs)

Abdulkerim Eroglu (Department of Human Nutrition, Ohio State University), Damian Hruszkewycz (College of Pharmacy, Ohio State University), Robert W. Curley (College of Pharmacy, Ohio State University), Earl H. Harrison (Department of Human Nutrition, Ohio State University)

Abstract:
β-carotene (BC) is the major dietary source of provitamin A. Two pathways were described for the cleavage of BC: central (symmetric) cleavage and eccentric (asymmetric) cleavage. β-carotene oxygenases (BCOs) are the enzymes involved in cleavage of BC. Central cleavage of BC catalyzed by BCO1 yields two molecules of retinal followed by further oxidization to retinoic acid. Eccentric cleavage of BC is catalyzed by BCO2. The polyene chain of BC is cleaved at double bonds other than the central double bond and the products of this pathway are β-apo-carotenals and β-apo-carotenones with different chain lengths. Retinoids are involved in embryonic development, the control of cell proliferation, and cell differentiation. They exert these functions through three retinoic acid-activated nuclear receptor subtypes (RARα, RARβ, RARγ) by binding to them and eventually activating transcription of genes containing retinoic acid response elements (RAREs) in their promoters. The most potent endogenous retinoid is all-trans retinoic acid (ATRA). It is the primary activator of RARs. The objective of this study is to determine the effects of apocarotenoids on RARs. We conducted transactivation assays to see whether apocarotenoids activate or antagonize RARs. Reporter gene constructs (pRARE-Luc, pRL-tk) and retinoic acid receptor subtypes (RARα, RARβ, RARγ) were transfected into COS-1 cells which were used to perform quantitative assays for the activation of these ligand dependent transcription factors. None of the compounds so far tested activated these transcription factors. However, three compounds (β-apo-8’-carotenoic acid, β-apo-14’-carotenoic acid, and β-apo-13-carotenone) antagonize ATRA activation of RARs. These findings shed light on the possible mechanisms of action of apocarotenoids.

Keywords: Beta-carotene oxygenases, Beta-apo-carotenones, Beta-apo-carotenals, Retinoic Acid Receptors