Yong V W, Dooley N P, Noble P G
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.
J Neurosci Res. 1994 Sep 1;39(1):83-96. doi: 10.1002/jnr.490390111.
The extension of cellular processes from the oligodendrocyte soma is an early and critical event in myelin formation. Previous reports from this laboratory have implicated a role for protein kinase C (PKC) as an important intracellular mediator of this critical step in myelinogenesis. In the current study, the regrowth of fibers by adult human oligodendrocytes was examined and was found to be significantly enhanced by 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 oligodendrocytes was not followed by subsequent down-regulation of the enzyme. The role of PKC in oligodendroglial process formation was further demonstrated by the ability of inhibitors of PKC to block the basal- or PDB-enhanced fiber outgrowth. As well, studies employing isoform-specific agonists implicated PKC alpha as the major determinant of fiber outgrowth by oligodendrocytes. The potential significance of PKC in myelin formation was further underscored by the observation that the synthesis of myelin basic protein, a prerequisite component for myelinogenesis, was increased by 2-fold in PDB-treated oligodendrocytes. Collectively, these observations suggest that PKC, in particular the alpha isoform, constitutes an important mediator in the initiation of myelin formation.
少突胶质细胞胞体延伸出细胞突起是髓鞘形成过程中早期且关键的事件。本实验室之前的报告表明蛋白激酶C（PKC）作为髓鞘形成这一关键步骤的重要细胞内介质发挥作用。在当前研究中，对成人少突胶质细胞的纤维再生进行了检测，发现PKC刺激剂4β-佛波醇-12,13-十四酸酯（PDB）可显著增强其纤维再生；同时少突胶质细胞的PKC活性增加了400%-500%。与其他细胞类型不同，少突胶质细胞中PKC活性增加后并未伴随该酶的后续下调。PKC抑制剂能够阻断基础状态或PDB增强的纤维生长，这进一步证明了PKC在少突胶质细胞突起形成中的作用。此外，使用亚型特异性激动剂的研究表明PKCα是少突胶质细胞纤维生长的主要决定因素。PDB处理的少突胶质细胞中髓鞘生成的前提成分髓鞘碱性蛋白的合成增加了2倍，这一观察结果进一步强调了PKC在髓鞘形成中的潜在重要性。总的来说，这些观察结果表明PKC，尤其是α亚型，是髓鞘形成起始过程中的重要介质。
