Differential role of specific PKC isoforms in the proliferation of glial cells and the expression of the astrocytic markers GFAP and glutamine synthetase.
In this study, we explored the role of specific protein kinase C (PKC) isoforms in glial cell proliferation and on the expression of the astrocytic markers GFAP and glutamine synthetase using C6 cells as a model. Analysis of the expression of the various PKC isoforms in control and differentiated C6 cells revealed differences in the expression of specific PKC isoforms. Undifferentiated C6 cells, which express low levels of GFAP and glutamine synthetase (GS), have high levels of PKCalpha and delta, whereas differentiated C6 cells, which express higher levels of both GFAP and GS have lower levels of PKCalpha and delta and higher levels of PKCgamma, theta and eta. Using C6 cells overexpressing specific PKC isoforms, we examined the role of these isoforms on the proliferation and differentiation of C6 cells. Cells overexpressing PKCalpha displayed a reduced level of GFAP, whereas GS expression was not affected. On the other hand, cells overexpressing PKCdelta showed reduced GS expression but little effect on GFAP. Finally, cells expressing PKCgamma displayed a marked increase in the levels of both GFAP and GS. The proliferation of C6 cells was increased in cells overexpressing PKCalpha and epsilon and decreased in cells overexpressing PKCgamma, delta and eta. The results of this study suggest that glial cell proliferation and astrocytic differentiation can be regulated by specific PKC isoforms that selectively affect cell proliferation and the expression of the two astrocytic markers GFAP and GS.
Brodie
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Molecular Mechanisms of Tumor Promotion Section, LCCTP, NCI, NIH, Bethesda, MD 20892, USA. brodiec@dc37.nci.nih.gov
Kuperstein
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Acs
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Blumberg
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D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D005910:Glioma; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010641:Phenotype; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D020033:Protein Isoforms; D011493:Protein Kinase C; D005974:Glutamate-Ammonia Ligase