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Regulation of hepatic lecithin:retinol acyltransferase activity by retinoic acid receptor-selective retinoids.

Authors: Shimada, T  Ross, AC  Muccio, DD  Brouillette, WJ  Shealy, YF 
Citation: Shimada T, etal., Arch Biochem Biophys. 1997 Aug 1;344(1):220-7.
Pubmed: (View Article at PubMed) PMID:9244401
DOI: Full-text: DOI:10.1006/abbi.1997.0209

The microsomal enzyme LRAT esterifies retinol and has been implicated in the hepatic storage of vitamin A. Previously, we showed that hepatic LRAT activity is negligible during vitamin A deficiency and that all-trans-retinoic acid (all-trans-RA) rapidly induces the activity of liver LRAT in retinoid-deficient rats. In the present studies, we have examined the ability of natural and synthetic retinoids to induce liver LRAT activity in retinoid-deficient rats. The natural retinoids retinol, all-trans-RA (100 microg), 9-cis-RA, or equal molar amounts of other retinoids were injected ip and LRAT specific activity was measured in liver homogenates 17-18 h later. In retinoid-deficient rats, liver LRAT activity was extremely low [0.13 +/- 0.03 pmol retinyl ester (RE)/min/mg liver protein, mean +/- SE]. The natural retinoids retinol and all-trans-RA strongly induced LRAT activity (12.71 +/- 1.09 and 13.10 +/- 1.55 pmol RE/min/mg, respectively), whereas 9-cis-RA induced a lower level of LRAT activity (3.96 +/- 1.88 pmol RE/min/mg, P < 0.001 vs all-trans-RA). The retinoic acid receptor (RAR)-selective analog (RAR pan-agonist) all-trans-UAB8 and the RAR-alpha-selective retinoid Am580 also strongly induced LRAT activity. In contrast, neither RXR-selective agonists nor retinoids having a retro structure were active. For retinoids with significant RAR-alpha binding activity there was a strong direct correlation between receptor binding in vitro and the ability to induce hepatic LRAT activity in vivo (r2 = 0.920). These data implicate the RARs in the induction of hepatic LRAT and suggest a predominant role for RAR-alpha-active ligands.

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CRRD Object Information
CRRD ID: 1599832
Created: 2007-02-16
Species: All species
Last Modified: 2007-02-16
Status: ACTIVE



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