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Effects of retinoid catabolism on the gene expression in primary rat hepatocytes and hepatoma cells
Author(s) -
Li Yang,
Chen Guoxun
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1015.1
Subject(s) - retinoic acid , retinoid , retinoid x receptor , catabolism , gene expression , retinol , biology , retinoic acid receptor , hepatocyte , retinoid x receptor alpha , endocrinology , microbiology and biotechnology , chemistry , nuclear receptor , biochemistry , gene , metabolism , vitamin , transcription factor , in vitro
Vitamin A (retinol, ROL) is reversibly oxidized into retinal (RAL) by retinol dehydrogenases; retinal is irreversibly oxidized by retinal dehydrogenases into retinoic acid (RA) in cells. RA regulates gene expression via activation of retinoic acid receptor (RAR) and retinoid X receptor (RXR). We have shown that retinoids synergize with insulin to induce Srebp‐1c expression in primary rat hepatocytes. Therefore, we hypothesize that RA production controls the regulation of hepatic gene expression. The expression of Cyp26a1 (an RA responsive gene) was examined using real‐time PCR and used as a marker for RA production from ROL and RAL in primary hepatocytes and hepatoma cells. Here, we show that retinol and retinal dose‐dependently induced Cyp26a1 expression via activation of RAR and RXR in those cells. The expression levels of Rdh2 , Rdh10 , Raldh1 , and Raldh3 (major retinoid catabolic enzymes) were examined in hepatocytes from Zucker lean (ZL) and fatty (ZF) rats. Only Rdh2 and Raldh1 were expressed at comparable level as that of 36B4 gene (the invariable control gene) in hepatocytes and hepatoma cells. In addition, the hepatocytes from ZF rats had higher expression level of Raldh1 than that from ZL rats. We conclude that hepatocytes actively metabolize retinol into RA, which directly regulate gene expression. The elevated Raldh1 expression in ZF hepatocytes may contribute to the altered lipid metabolism in ZF liver. Sponsor: Guoxun Chen, 1215 W. Cumberland Ave. 229 Jessie Harris Building, Knoxville, TN 37996Grant Funding Source : AHA