PROTEIN-KINASE-C IN CULTURED ADULT HUMAN OLIGODENDROCYTES - A POTENTIAL ROLE FOR ISOFORM A AS A MEDIATOR OF PROCESS OUTGROWTH

The extension of cellular processes from the oligodendrocyte soma is a n early and critical event in myelin formation. Previous reports from this laboratory have implicated a role for protein kinase C (PKC) as a n important intracellular mediator of this critical step in myelinogen esis. In the current study, the regrowth of fibers by adult human olig odendrocytes was examined and was found to be significantly enhanced b y the PKC stimulator, 4 beta-phorbol-12,13-didecanoate (PDB); this was accompanied by a 400-500% increase in oligodendroglial PKC activity. In contrast to other cell types, the increased PKC activity in oligode ndrocytes was not followed by subsequent down-regulation of the enzyme . The role of PKC in oligodendroglial process formation was further de monstrated by the ability of inhibitors of PKC to block the basal- or PDB-enhanced fiber outgrowth. As well, studies employing isoform-speci fic agonists implicated PKC alpha as the major determinant of fiber ou tgrowth by oligodendrocytes. The potential significance of PKC in myel in formation was further underscored by the observation that the synth esis of myelin basic protein, a prerequisite component for myelinogene sis, was increased by 2-fold in PDB-treated oligodendrocytes. Collecti vely, these observations suggest that PKC, in particular the alpha iso form, constitutes an important mediator in the initiation of myelin fo rmation. (C) 1994 Wiley-Liss, Inc.