Transcription factor expression and cellular redox in immature oligodendrocyte cell death: effect of Bcl-2.
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.
FitzGerald
Una F
UF
Department of Neurology and Department of Medical Oncology, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland.
Gilbey
Tom
T
Brodie
Suzanne
S
Barnett
Susan C
SC
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D016923:Cell Death / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002518:Ceramides / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005949:Glucose Oxidase / Q000494:pharmacology; D005978:Glutathione / Q000096:biosynthesis; D017874:Immediate-Early Proteins; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D002518:Ceramides; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D020126:Brefeldin A; D005949:Glucose Oxidase; D005978:Glutathione