Regulation of hepatic lecithin:retinol acyltransferase activity by retinoic acid receptor-selective retinoids.
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.
Shimada
T
T
Department of Nutrition, The Pennsylvania State University, University Park 16802, USA.
Ross
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D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D005260:Female; D008862:Microsomes, Liver / Q000201:enzymology*; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D014801:Vitamin A; D014212:Tretinoin; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase