The regulation of glutamine synthetase gene expression in cultured rat astrocytes and its differential regulation with glycerol phosphate dehydrogenase in C6 glioma cells.

摘要

The hormonal regulation of two astrocyte marker proteins, glutamine synthetase (GS, E.C.6.3.1.2) and glial fibrillary acidic protein, was examined in cultures of astrocytes from neonatal rat cerebrum. The regulation of glial-specific genes in the C6 rat glioma cell line was also studied.; In cultured astrocytes, hydrocortisone (HC), insulin, and thyroid hormone (T3) all enhanced the specific activity of GS following prolonged treatment. Only HC produced a significant increase in GS activity, protein, and mRNA levels following brief hormonal treatment. We conclude that insulin and T3 regulation of GS activity in astrocytes are indirect events, in contrast to the direct transcriptional regulation of GS by HC.; GS is an enzyme considered to be localized predominantly in astrocytes, whereas glycerol phosphate dehydrogenase (GPDH, E.C.1.1.1.8) is localized mainly in oligodendrocytes. In C6 cells, IL-6 induced GS enzymatic activity and decreased GPDH activity and mRNA. IFN and IL-6 also increased the amount of GFAP protein and mRNA. It was concluded that cytokines, such as IFN and IL-6 produce an astrocyte-like phenotype in C6 cells.; It was demonstrated that RA can promote an oligodendrocyte-like phenotype in the rat C6 glioma cell line. RA treatment caused a decrease in GS activity and an increase in GPDH activity and mRNA levels. RA reduces the HC- and forskolin-induced increase in GS activity. The results of the combined treatment of hydrocortisone and forskolin with retinoic acid on GS activity in C6 cells suggest the hypothesis that HC, forskolin, and RA regulate transcription of the GS gene by acting at a common regulatory site.