Staurosporine induces astrocytic phenotypes and differential expression of specific PKC isoforms in C6 glial cells.
In this study we examined the effects of staurosporine, a potent inhibitor of protein kinase C (PKC), on the differentiation of C6 glial cells and on the expression and cellular distribution of specific PKC isoforms. Staurosporine reduced cell proliferation and induced distinctive changes in the morphological appearance of the cells to that characteristic of cells exhibiting astrocytic phenotypes. The differentiative effect of staurosporine was further indicated by the increased expression of two proteins related to astrocytic phenotypes, glial fibrillary acidic protein (GFAP) and glutamine synthetase. Thus, staurosporine induced a dose-dependent increase both in GFAP immunoreactivity and in the activity and protein levels of glutamine synthetase. Staurosporine also induced a decrease in the expression of PKC-beta 2 and an increase in that of PKC-gamma. In addition, it induced translocation of PKC-epsilon from the membrane to the cytosol, whereas no differences were observed in the distribution of the other PKC isoforms. The results of our study indicate that staurosporine induced astrocytic phenotypes in glial cells and that changes in the expression and cellular distribution of these PKC isoforms may be related to astrocytic differentiation.
Kronfeld
I
I
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Zsukerman
A
A
Kazimirsky
G
G
Brodie
C
C
D000470:Alkaloids / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D019311:Staurosporine; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D011493:Protein Kinase C; D005974:Glutamate-Ammonia Ligase; D019311:Staurosporine