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Transcriptional‐ and post‐transcriptional‐dependent regulation of glutathione S ‐transferase expression in rat hepatocytes as a function of culture conditions
Author(s) -
Vandenberghe Yves,
Tee Lisa,
Rogiers Vera,
Yeoh George
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81434-n
Subject(s) - microbiology and biotechnology , in vitro , hepatocyte , gene expression , biology , glutathione , nicotinamide , glutathione s transferase , transcriptional regulation , fetus , cell culture , gene , transcription (linguistics) , biochemistry , enzyme , genetics , pregnancy , linguistics , philosophy
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.