Transcription factor expression and cellular redox in immature oligodendrocyte cell death: effect of Bcl-2

FitzGerald, U. F., Gilbey, T., Brodie, S. and Barnett, S. C. (2003) Transcription factor expression and cellular redox in immature oligodendrocyte cell death: effect of Bcl-2. Molecular and Cellular Neuroscience, 22(4), pp. 516-529. (doi: 10.1016/S1044-7431(02)00040-4) (PMID:12727447)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barnett, Professor Susan
Authors: FitzGerald, U. F., Gilbey, T., Brodie, S., and Barnett, S. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular and Cellular Neuroscience
Publisher:Elsevier
ISSN:1044-7431
ISSN (Online):1095-9327
Published Online:08 February 2003

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