Reactive oxygen intermediates in TNF signaling.

Tumor necrosis factor (TNF) is arguably the most potent inducer of several intracellular signals, including apoptosis, cell differentiation, and gene transcription. It does so through the activation of caspases, specific kinases including mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), transcription factors Activated protein 1 (AP-1), and nuclear factor kappa-B (NF-kappaB). By activating these signals, TNF mediates pro-apoptotic and pro-survival mechanisms in the cell. It has also been suggested that TNF mediates its intracellular signaling by adjusting the redox potential of the cell, specifically through reactive oxygen intermediates (also known as reactive oxygen species). Here we review the evidence linking ROI to TNF-induced signaling and propose that ROI mediate both pro-apoptotic and pro-survival signals. How these antagonistic signals are balanced to maintain homeostasis is still not clear.