OXIDATIVE STRESS AND HYPOXIA REOXYGENATION TRIGGER CD95 (APO-1/FAS) LIGAND EXPRESSION IN MICROGLIAL CELLS/

Apoptosis plays an important role in neurodegeneration, although the m echanisms and mediators in the brain are largely unknown. Because micr oglial cells have been suggested to contribute to apoptosis in neurolo gical disorders, we investigated the expression of the death ligand CD 95L in this cell type. We found that, compared to classical mediators of microglial activation, the most potent inducer of CD95L mas oxidati ve stress. Exposure of microglial cells to H2O2 or paraquat rapidly tr iggered CD95L mRNA and protein expression, associated with the activat ion of transcription factor NF-kappa B. Enhanced expression of CD95L m as further found following exposure of cells to hypoxia and subsequent reoxygenation, Our results indicate a potential role of CD95L in oxid ative stress-mediated cell death, ischemia/reperfusion and other disea ses with a disturbed redox balance. (C) 1998 Federation of European Bi ochemical Societies.