Oxidative Stress Kills Human Primary Oligodendrocytes Via Neutral Sphingomyelinase: Implications for Multiple Sclerosis
- 8 March 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Neuroimmune Pharmacology
- Vol. 2 (2), 184-193
- https://doi.org/10.1007/s11481-007-9066-2
Abstract
Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system where oxidative stress has been proposed to play an important role in oligodendroglial death. However, molecular mechanisms that couple oxidative stress to the loss of oligodendrocytes are poorly understood. This study underlines the importance of neutral sphingomyelinase–ceramide pathway in mediating oxidative stress-induced apoptosis and cell death of human primary oligodendrocytes. Various oxidative stress-inducing agents, such as, superoxide radical produced by hypoxanthine and xanthine oxidase, hydrogen peroxide, aminotriazole capable of inhibiting catalase and increasing intracellular level of H2O2, or reduced glutathione-depleting diamide induced the activation of neutral sphingomyelinase and the production of ceramide. It is interesting to note that antisense knockdown of neutral but not acidic sphingomyelinase ablated oxidative stress-induced apoptosis and cell death in human primary oligodendrocytes. This study identifies neutral but not acidic sphingomyelinase as a target for possible therapeutic intervention in MS.Keywords
This publication has 32 references indexed in Scilit:
- nSMase2 activation and trafficking are modulated by oxidative stress to induce apoptosisBiochemical and Biophysical Research Communications, 2006
- Redox regulation of cytokine-mediated inhibition of myelin gene expression in human primary oligodendrocytesFree Radical Biology & Medicine, 2005
- Human Immunodeficiency Virus Type 1 gp120 Induces Apoptosis in Human Primary Neurons through Redox-Regulated Activation of Neutral SphingomyelinaseJournal of Neuroscience, 2004
- Mitochondrial pathway is involved in hydrogen‐peroxide‐induced apoptotic cell death of oligodendrocytesGlia, 2004
- Regulation of sphingomyelinases in cells of the oligodendrocyte lineageJournal of Neuroscience Research, 2003
- Glutathione Regulation of Neutral Sphingomyelinase in Tumor Necrosis Factor-α-induced Cell DeathPublished by Elsevier BV ,1998
- Sphingomyelinase and Ceramide Stimulate the Expression of Inducible Nitric-oxide Synthase in Rat Primary AstrocytesPublished by Elsevier BV ,1998
- Functions of Ceramide in Coordinating Cellular Responses to StressScience, 1996
- Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in PathogenesisBrain Pathology, 1996
- Ceramide Induces Apoptosis in Cultured Mesencephalic NeuronsJournal of Neurochemistry, 1996