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

Takaki Shimada, A. Catharine Ross, Donald D. Muccio, Wayne J. Brouillette, Y. Fulmer Shealy

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Abstract

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 μg), 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) alltrans-UAB8 and the RAR-α-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-α 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-α-active ligands.

Original languageEnglish (US)
Pages (from-to)220-227
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume344
Issue number1
DOIs
Publication statusPublished - Aug 1 1997

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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