Protein Kinase C Activation Drives a Differentiation Program in an Oligodendroglial Precursor Model through the Modulation of Specific Biological Networks

Abstract

Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography–mass spectrometry (LC–MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.

Effects Mediated by Dimethyl Fumarate on In Vitro Oligodendrocytes: Implications in Multiple Sclerosis

“…By RT-PCR analysis, we observed that the treatment with 25 μM DMF for 24 h induced a significant reduction in the Cx-32 expression compared with the control ( Figure 4 g). A recent study supported the involvement of protein kinase Cα (PKCα) in glial cell maturation and myelination [ 45 ]. The activation of PKCα has been found to drive a gliogenesis program associated with the modulation of several biological processes, including remodeling of the cytoskeleton, which is critical in the formation of differentiation processes [ 45 , 46 , 47 ].…”

“…A recent study supported the involvement of protein kinase Cα (PKCα) in glial cell maturation and myelination [ 45 ]. The activation of PKCα has been found to drive a gliogenesis program associated with the modulation of several biological processes, including remodeling of the cytoskeleton, which is critical in the formation of differentiation processes [ 45 , 46 , 47 ]. Western blot analysis showed that 24 h of treatment with 25 μM DMF induced a significant increase in PKCα expression compared with the control (DMSO) ( Figure 4 h), supporting the hypothesis of a pro-differentiative effect of DMF in Oli neu cells.…”

“…We found that DMF treatment induced an increase in MBP transcript expression, while it reduced the transcript levels of CX-32 . Another factor whose role in glial cell maturation and myelination has recently been discovered is PKCα [ 45 ]. Western blot analysis showed that after 24 h of treatment with DMF, an increase in PKCα protein expression was observed in Oli neu cells compared to the control condition ( Figure 4 h).…”

Analysis of Signal Transduction Pathways Downstream M2 Receptor Activation: Effects on Schwann Cell Migration and Morphology

“…It is known that various PKC isoforms drive a glycogenesis program mediating cytoskeletal remodeling, cell cycle control and metabolism modifications [35,36]. APE treatment leads to cytoskeletal modifications, with changes in cell morphology and redistribution of adhesion molecules [10].…”

“…It is known that PKC-α sits at the crossroads of many signal transduction pathways and is implicated in a wide range of cellular responses. Various PKC isoforms drive a glycogenesis program associated with cytoskeletal remodeling, cell cycle control and metabolism modifications [35,36]. As shown in Figure 3A, APE treatment caused a significant increase in PKCα kinase protein levels compared to the untreated cells.…”