Abstract
Multiple sclerosis (MS) is characterized by the progressive damage or loss of oligodendrocytes. In an effort to better understand the causes of oligodendrocyte destruction in MS plaques, we treated immature oligodendrocytes with glucose oxidase, ceramide, or brefeldin A. These treatments model the different mechanisms by which oligodendrocytes are thought to die. We report that the AP-1 and Egr-1 transcription factors are induced within an hour of treatment. Of the AP-1 proteins studied, c-Jun was expressed at the highest level, followed by JunD, c-Fos, and Fra-2, although different treatments induced slightly different levels of expression. Bcl-2 overexpression protects against all treatments, to differing degrees. Although Bcl-2 did not have a dramatic effect on AP-1 or Egr-1 induction within the first 3 h, it caused a lowering of steady-state redox levels with a concomitant increase in cellular glutathione. We propose that the lowering of cellular redox and the upregulation of glutathione are responsible in part for the protective properties of Bcl-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brefeldin A / pharmacology
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Cell Death / genetics*
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Line
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Central Nervous System / metabolism*
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Central Nervous System / pathology
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Central Nervous System / physiopathology
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Ceramides / pharmacology
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DNA-Binding Proteins / drug effects
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DNA-Binding Proteins / metabolism
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Early Growth Response Protein 1
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Glucose Oxidase / pharmacology
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Glutathione / biosynthesis
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Immediate-Early Proteins*
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Multiple Sclerosis / genetics*
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Multiple Sclerosis / metabolism
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Oligodendroglia / metabolism*
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Oligodendroglia / pathology
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Oxidation-Reduction / drug effects
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Proto-Oncogene Proteins c-jun / drug effects
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Proto-Oncogene Proteins c-jun / metabolism
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Rats
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Stem Cells / metabolism*
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Stem Cells / pathology
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Transcription Factor AP-1 / drug effects
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Transcription Factor AP-1 / metabolism
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Transcription Factors / drug effects
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Transcription Factors / metabolism*
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Ceramides
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DNA-Binding Proteins
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Early Growth Response Protein 1
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Egr1 protein, rat
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Immediate-Early Proteins
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-jun
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Transcription Factor AP-1
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Transcription Factors
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Brefeldin A
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Glucose Oxidase
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Glutathione