Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand expression in microglial cells.

Apoptosis plays an important role in neurodegeneration, although the mechanisms and mediators in the brain are largely unknown. Because microglial cells have been suggested to contribute to apoptosis in neurological disorders, we investigated the expression of the death ligand CD95L in this cell type. We found that, compared to classical mediators of microglial activation, the most potent inducer of CD95L was oxidative stress. Exposure of microglial cells to H2O2 or paraquat rapidly triggered CD95L mRNA and protein expression, associated with the activation of transcription factor NF-kappaB. Enhanced expression of CD95L was further found following exposure of cells to hypoxia and subsequent reoxygenation. Our results indicate a potential role of CD95L in oxidative stress-mediated cell death, ischemia/reperfusion and other diseases with a disturbed redox balance.