Retinoid‐mediated CYP26a1 expression in primary rat hepatocytes and hepatoma cells

Abstract

Vitamin A (or retinol) plays a crucial role in health of humans as a micronutrient. Recently we have shown that retinoid synergize with insulin to induce Gck gene expression in primary rat hepatocytes. Based on data from us and others, we believe that VA may be involved in glucose and lipid metabolism in humans.In cells, retinol (ROL) is reversibly oxidized into retinal (RAL) by retinol dehydrogenase (RDH) and irreversibly into retinoic acid (RA), which is the activator of nuclear receptors‐retinoic acid receptor (RAR) and retinoid X receptor (RXR). We hypothesize that cells may respond to ROL, RAL, and RA depending on the catabolic enzymes of retinoid existing in them. Therefore, we determined and compared the expression levels of CYP26a1, a RA responsive gene, in response to retinoids in both primary rat hepatocytes and HL1C, a rat hepatoma cell line.We observed that ROL, RAL and RA induced expression of CYP26a1 gene in both primary rat hepatocytes and HL1C cells in a dosage dependent manner. RAL and RA induced the expression of CYP26a1 as early as 3 hours and peaked at 9 hours. In addition, we examined the expression levels of RDH and RALDH in primary hepatocytes and HL1C cells. We found that both types of cells have comparable levels of RDH2 and RALDH1 expression. We are currently trying to confirm their roles in mediating the retinoid catabolism and retinoid‐mediated gene expression in different types of cells.Sponsor: Guoxun Chen, 1215 W. Cumberland Ave. 229 Jessie Harris Building, Knoxville, TN37996