All-trans-retinol is a ligand for the retinoic acid receptors.

Abstract

Competition of all-trans-retinol and all-trans-retinaldehyde with 3H-labeled all-trans-retinoic acid (RA) for binding to retinoic acid receptors (RARs) was examined in human neuroblastoma cell nuclear extracts. All-trans-retinol was 35-fold less potent than all-trans-RA, whereas all-trans-retinaldehyde was 500-fold less active in binding to the nuclear receptors. To confirm that all-trans-retinol binds to RARs, experiments were carried out with RARs alpha, beta, and gamma expressed as bacterial fusion proteins. All-trans-retinol was only 4- to 7-fold less potent than all-trans-RA in binding to all three RAR subtypes. The all-trans-retinol binding observed was not the result of metabolism of retinol to RA or some other active compound during the binding experiment. Retinyl acetate was virtually inactive in competition binding experiments, while very slight activity was observed with 13-cis-RA and all-trans-retinaldehyde. Significant competition occurred with 4-hydroxy-RA and 4-keto-RA, which were 15- to 40-fold less potent than all-trans-RA. The 9-cis isomer of RA was equipotent with all-trans-retinol in these studies. These results suggest that all-trans-retinol cannot be excluded as a physiologically significant ligand for RAR-mediated gene expression.

Induction of the oxidative catabolism of retinoic acid in MCF-7 cells

“…In RbTE cells and HL-60 leukaemia cells, the biological activity of the synthetic retinoid CH55 was much higher (20-25 times) than that of all-trans-RA (Jetten et al, 1987). Overall, the RA catabolism-inducing capacity of the different retinoids correlates with the retinoic acid receptor binding affinities of the retinoids (Crettaz et al, 1990;Sani et al, 1990;Repa et al, 1993;Berggren Soderhund et al, 1995), suggesting that induction of RA catabolism is a receptor-mediated process. Two other lines of evidence substantiate this idea.…”

Efficient Induction of CCR9 on T Cells Requires Coactivation of Retinoic Acid Receptors and Retinoid X Receptors (RXRs): Exaggerated T Cell Homing to the Intestine by RXR Activation with Organotins

“…The following possibilities can be considered: a yet-to-be discovered endogenous RXR ligand is present; 9-cis-RA is produced and catabolized in a strictly regulated fashion; and RXR ligands with high affinity, such as 9-cis-RA, are produced only spontaneously from physiological retinoids by isomerization and/or dehydrogenation. If one of the latter two possibilities were true, direct RXR stimulation could be limited in vivo, and exogenous RXR agonists might easily exaggerate CCR9 expression on T cells in the presence of low levels of RA or physiological levels of retinol that could weakly bind to RAR (38).…”

“…The weak effect of 100 nM PA024 alone on CCR9 expression was inhibited by the RAR antagonist LE540 (Fig. 2F), suggesting that PA024 might also exert a weak RAR-activating effect by itself or that weak RAR-stimulating molecules, such as retinol in the culture medium (38), might synergize with PA024. The latter possibility might be involved, Fig.…”

Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors

“…Specific binding was determined by a hydroxyapatite-binding assay (14). ␤-Apocarotenoids Are RAR Antagonists tion constants (K d ) and inhibition constants (K i ) were determined using GraphPad Prism (version 5.0) with non-linear regression.…”