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 ast rocytic markers GFAP and,glutamine synthetase using C6 cells as a mode l. Analysis of the expression of the various PKC isoforms in control a nd differentiated C6 cells revealed differences in the expression of s pecific PKC isoforms. Undifferentiated C6 cells, which express low lev els of GFAP and glutamine synthetase (GS), have high levels of PKC alp ha and delta, whereas differentiated C6 cells, which express higher le vels of both GFAP and GS have lower levels of PKC alpha and delta and higher levels of PKC gamma, theta and eta. Using C6 cells overexpressi ng specific PKC isoforms, we examined the role of these isoforms on th e proliferation and differentiation of C6 cells. Cells overexpressing PKC alpha displayed a reduced level of GFAP, whereas GS expression was not affected. On the other hand, cells overexpressing PKC delta showe d reduced GS expression but little effect on GFAP. Finally, cells expr essing PKC gamma displayed a marked increase in the levels of both GFA P and GS. The proliferation of C6 cells was increased in cells overexp ressing PKC alpha and epsilon and decreased in cells overexpressing PK C gamma, delta and eta. The results of this study suggest that glial c ell proliferation and astrocytic differentiation can be regulated by s pecific PKC isoforms that selectively affect cell proliferation and th e expression of the two astrocytic markers GFAP and GS. (C) 1998 Elsev ier Science B.V.