FIG. 8.

Relationship between intracellular redox status and activity of effectors of TNF-α signaling. The outcome of TNF-α signaling in hepatocytes (i.e., proliferation/survival, apoptosis, or necrosis, Fig. 7) is strongly influenced by the intracellular redox status, which can range from highly reduced (in green) to severely oxidized (in red). The graph depicts how the activity of key components of the TNF-α signaling cascade (i.e., JNK, caspase 8, and NF-κB) is influenced by the intracellular redox status. When the intracellular environment is sufficiently reduced, the effects of NF-κB will prevail, resulting in cell proliferation/survival. However, if the cellular redox status shifts toward a more oxidized state, NF-κB signaling is inhibited such that activated JNK and caspase 8 signal transduction pathways can be actualized, resulting in apoptosis. When the intracellular environment becomes severely oxidized, ROS/RNS-dependent necrotic cell death ensues because of the sustained activation of JNK and possibly caspase 8 inactivation. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars