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Depolarizing agents and tumor necrosis factor‐α modulate protein phosphorylation in oligodendrocytes
Author(s) -
Soliven B.,
Takeda M.,
Szuchet S.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490380112
Subject(s) - phosphorylation , depolarization , microbiology and biotechnology , biology , myelin basic protein , oligodendrocyte , protein phosphorylation , myelin , protein kinase a , chemistry , biophysics , neuroscience , central nervous system
Membrane depolarization and changes in ionic fluxes have been implicated in the signaling mechanisms between neurons and glial cells . We report here that K + ‐induced depolarization of cultured ovine oligodendrocytes (OLGs) decreases the phosphorylation of myelin basic protein (MBP) and 2′3′‐cyclic nucleotide phosphohydrolase (CNPase). Membrane depolarization and decrease in phosphorylation of MBP and CNPase can also be elicited by inhibition of the inward rectifier with Ba 2+ but not by inhibition of outward K + channels with 4‐aminopyridine or tetraethylammonium. These findings demonstrate that modulation of K + currents can influence phosphorylation states of OLG proteins. Tumor necrosis factor‐α (TNF‐α), an immune peptide implicated in autoimmune demyelinating diseases, also inhibits the phosphorylation of these proteins. In contrast to elevated [K + ] 0 , TNF‐α does not decrease the stimulatory effect of protein kinase C activators or phosphatase inhibitors on MBP and CNPase phosphorylation, suggesting that depolarizing agents and TNF‐α act via distinct mechanisms. We postulate that the presence of elevated extracellular K + and/or cytokines under certain pathological conditions can perturb OLG function by altering the phosphorylation states of their proteins and perhaps affect myelin maintenance, contributing to demyelination. © 1994 Wiley‐Liss, Inc.