Mol Cell Neurosci 2003 Apr;22(4):516-29
FitzGerald UF, Gilbey T, Brodie S, Barnett SC.
Department of Neurology and Department of Medical Oncology, Garscube Estate, Switchback Road, G61 1BD, Glasgow, Scotland
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.