Transcriptional-dependent and Post-transcriptional-dependent Regulation of Glutathione-s-transferase Expression in Rat Hepatocytes As a Function of Culture Conditions
Transcriptional activity of the glutathione S-transferase (GST) alpha (subunits 1 and 2), mu (subunits 3 and 4) and pi (subunit 7) gene families has been analyzed using the nuclear 'run-on' technique on adult rat hepatocytes maintained for 4 days in conventional culture and for 4 and 12 days in co-culture with rat liver epithelial cells. Several medium conditions are included in this study, namely with or without fetal calf serum and with nicotinamide or dimethylsulphoxide. Hepatocytes co-cultured for 4 days maintain approximately 30-70% of the alpha gene family transcriptional activity, whatever the medium conditions, when compared to freshly isolated hepatocytes. A marked decrease is observed after 12 days of co-culture or when hepatocytes are maintained in conventional culture. The transcriptional activity of the mu gene family is maintained at 40-160% when hepatocytes are cultured with or without fetal calf serum, and is inducible by nicotinamide (approximately 4-fold) and dimethylsulphoxide (approximately 2-fold) in conventional culture and/or in co-culture. In contrast to freshly isolated hepatocytes, GST pi gene transcriptional activity is observed in conventional and co-cultured hepatocytes, irrespective of the medium conditions. Dimethylsulphoxide treatment however, represses the expression of GST 7 in vitro. These results demonstrate that the expression of GST alpha, mu and pi genes in conventional and co-cultured rat hepatocytes is controlled primarily at the level of transcription. It cannot be excluded, however, that dimethylsulphoxide stabilizes the GST mRNA levels in vitro.
Vandenberghe, Y., Tee, L., Rogiers, V., & Yeoh, G. (1992). Transcriptional-dependent and Post-transcriptional-dependent Regulation of Glutathione-s-transferase Expression in Rat Hepatocytes As a Function of Culture Conditions. FEBS Letters, 313(2), 155-159. https://doi.org/10.1016/0014-5793(92)81434-N (Original work published 1992)