Transcriptional- and post-transcriptional-dependent regulation of glutathione S-transferase expression in rat hepatocytes as a function of culture conditions

• Published in: FEBS letters Vol. 313; no. 2; pp. 155 - 159
• Main Authors: Vandenberghe, Yves, Tee, Lisa, Rogiers, Vera, Yeoh, George
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 23-11-1992; Elsevier
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Culture; Dimethyl Sulfoxide - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic; Glutathione S-transferase; Glutathione Transferase - genetics; Hepatocyte; Liver - metabolism; Male; Molecular and cellular biology; Molecular genetics; Rat; Rats; Rats, Sprague-Dawley; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional activity; Rat; Hepatocyte; Glutathione S-transferase; Transcriptional activity; Culture; Culture medium; Transcription; Enzyme; Rodentia; Subunit; Vertebrata; Regulation(control); Mammalia; Messenger RNA; Gene; Glutathione transferase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)81434-N

Transcriptional activity of the glutathione
S-transferase (GST) α (subunits 1 and 2), μ (subunits 3 and 4) and π (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 α 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 μ 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 π 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 α, μ and π 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.