Redox regulation of apoptosis by members of the TNF superfamily.

Tumor necrosis factor (TNF), fibroblast-associated cell surface (Fas) ligand, and TNF-related apoptosisinducing ligand (TRAIL), all members of the TNF superfamily, are arguably the most potent inducers of cell death. These cytokines induce cell death through sequential recruitment by the death receptors TNFR1- associated death domain protein (TRADD), Fas-associated death domain protein (FADD), FADD-like interleukin-1beta-converting enzyme (FLICE), and downstream caspases. Increasing evidence indicates that mitochondria play a critical role in cytokine receptor-mediated apoptosis. There is also now ample evidence that apoptosis induced by TNF and its family members is mediated through the production of reactive oxygen intermediates (also known as reactive oxygen species). Here we review the evidence linking reactive oxygen intermediates to cytokine-induced cell death mediated by TNF-alpha/beta, Fas, TRAIL, TNF-like weak inducer of apoptosis (TWEAK), and vascular endothelial cell growth inhibitor (VEGI).