Do ROS Induce Apoptosis or Necrosis?
Under various pathological conditions such as ischemia, excessive amounts of accumulated ROS induce apoptosis or necrosis by activating the MAPK, caspase cascades, and /or by disrupting mitochondrial membrane potential.67 This contribution of ROS to apoptosis and necrosis is highly cell-type specific, and also depends on the amount of endogenously or exogenously generated ROS present. As ROS induce activation of the JNK cascade, apoptosis induced by ROS is likely to be dependent on the JNK-mediated mitochondria-dependent apoptotic pathway. Alternatively, ROS may act directly on the mitochondria, inducing the mitochondrial membrane permeability transition (mPT) and resulting in the release of apoptogenic factors, such as cytochrome c, apoptosis-inducing factor (AIF), and/or Smac/DIABLO.68, 69The mechanisms underlying ROS-induced necrosis have been highly debated. It is well known that TNF induces ROS-dependent necrosis in murine fibrosarcoma, L929 cells.70 Geldanamycin treatment induces
