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Activation of AP‐1 and Nuclear Factor‐κB Transcription Factors Is Involved in Hydrogen Peroxide‐Induced Apoptotic Cell Death of Olligodendrocytes
Author(s) -
Vollgraf Ulrich,
Wegner Michael,
RichterLandsberg Christiane
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0732501.x
Subject(s) - pyrrolidine dithiocarbamate , programmed cell death , dna fragmentation , apoptosis , transcription factor , deferoxamine , aurintricarboxylic acid , apoptotic dna fragmentation , chemistry , microbiology and biotechnology , junb , signal transduction , biology , nf κb , biochemistry , gene
: H 2 O 2 ‐induced onset and execution of programmed cell death in mature rat brain oligodendrocytes in culture is accompanied by the induction and nuclear translocation of the transcription factors AP‐1 and nuclear factor‐κB (NF‐κB), both of which have been discussed as regulators of cell death and survival. Supershift analysis of nuclear extracts indicated that the AP‐1 complex consists of c‐Jun, c‐Fos, JunD, and possibly JunB proteins, and that the NF‐κB complex contains p50, p65, and c‐Rel proteins. The first signs of DNA fragmentation were seen already during the first hour after the treatment. DNA fragmentation could be prevented by the antioxidants pyrrolidine dithiocarbamate and vitamin E, by the nuclease inhibitor aurintricarboxylic acid, and by preincubation with the iron chelator deferoxamine (DFO). Additionally, DFO protected oligodendrocytes from H 2 O 2 ‐induced cytotoxic effects as assessed by the MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay, and suppressed the formation of free radicals. DFO alone led to a slight increase and in combination with H 2 O 2 synergistically induced DNA‐binding activities of AP‐1 and NF‐κB in oligodendrocytes. Our data suggest that although low levels of H 2 O 2 directly activate AP‐1 and NF‐κB and might contribute to signal transduction pathways promoting cell survival, the formation and action of hydroxyl radicals promote cell death mechanisms that can be attenuated by the iron chelator DFO.