Negative regulation of Apo A-I gene expression by retinoic acid in rat hepatocytes maintained in a coculture system》.pdfVIP

Biochimica et Biophysica Acta 1391 1998 329–336 Negative regulation of Apo A-I gene expression by retinoic acid in rat hepatocytes maintained in a coculture system Laurence Berthou a , Sophie Langouet b , Pascale Grude a , Patrice Denefle a , Didier Branellec a , ¨ ´ ` Andre Guillouzo b, ´ a Department of Biotechnology, CRVA Rhone-Poulenc Rorer Gencell, Vitry-sur-Seine, France ˆ b Unite Detoxication et Reparation Tissulaire, INSERM U456, Faculte de Pharmacie and U49 INSERM, Hopital Pontchaillou, ´ ´ ´ ´ Rennes, France Received 25 November 1997; revised 18 December 1997; accepted 5 January 1998 Abstract Rat hepatocytes cocultured with rat liver epithelial cells RLEC were used to investigate the influence of all-trans retinoic acid RA on the regulation of apolipoproteins Apo A-I and A-II gene expression, the major protein constituent of high-density lipoproteins. In contrast to rat hepatocytes in conventional primary culture, Apo A-I and Apo A-II gene expression remained high and stable for several days in parenchymal cells in coculture. Treatment of cocultured rat hepatocytes with RA resulted in a specific decrease in Apo A-I mRNA levels whereas no marked difference in Apo A-II mRNA levels was observed. Such a negative effect of RA was already detected as early as 2 days of treatment and was effective for the entire ex