title: Signal transduction pathways in oligodendrocytes: role of tumor necrosis factor-alpha.
abstract: We have used a combination of electrophysiological and biochemical approaches to investigate the effects and the mechanisms of action of tumor necrosis factor-alpha (TNF-alpha) on cultured oligodendrocytes (OLGs). Our studies have led to the following conclusions: (1) prolonged exposure of mature ovine OLGs to TNF-alpha leads to inhibition of process extension, membrane depolarization and a decrease in the amplitudes of both inwardly rectifying and outward K+ currents; (2) brief exposure of OLGs to TNF-alpha does not elicit membrane depolarization or consistent changes in cytosolic Ca2+ levels; (3) incubation of OLGs with TNF-alpha for 1 hr results in inhibition of phosphorylation of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Ceramides, which have been shown to be effectors of TNF-alpha, are ineffective in inhibiting phosphorylation, whereas sphingomyelinase mimics TNF-alpha in this action. These observations suggest that other products of sphingomyelin hydrolysis may be the mediator(s) of TNF-alpha effect on protein phosphorylation. We have thus demonstrated that TNF-alpha can perturb the functions of OLGs via modulation of ion channels and of protein phosphorylation without necessarily inducing cell death. It is conceivable that modulation of ion channels and protein phosphorylation constitutes effective mechanisms for the participation of cytokines in signal transduction during myelination, demyelination and remyelination.
authors.affiliation: Department of Neurology, University of Chicago, Illinois 60637, USA.
authors.forename: B
authors.initials: B
authors.lastname: Soliven
authors.forename: S
authors.initials: S
authors.lastname: Szuchet
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D009836:Oligodendroglia / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha