Oxygen caspase activation

Garcia-Ruiz, C., Colell, A., Paris, R., and Femandez-Checa, J. C., 2000, Direct interaction of GD3 ganghoside with mitochondria generates reactive oxygen species followed by mitochondrial permeabihty transition, cytochrome c release, and caspase activation. Faseb J14 847-858. 

The essential role of cytochrome c release from injured mitochondria in the activation of caspase 9 has been alluded to above. This pathway is especially important in proapoptotic stimuli that are not initiated by surface receptors for apoptosis, such as UV irradiation, and may involve mitochondrial dependent pathways [83]. Continued respiration in the presence of an open mitochondrial pore may result in the generation of reactive oxygen species. Release of cytochrome c may be mediated by the opening of the mitochondrial FT pore, a non-selective channel whose composition is only partially defined [84]. Inhibitors of FT pore opening, such as cyclosporine, which binds to the adenine nucleotide translocator (ANT), a component of the FT pore, and bongkrekic acid, as well as Bcl-2, prevent cytochrome c release and inhibit apoptosis [85] whereas activators of the FT pore, such as atractyloside and Bax induce it [86]. Oxidants can rupture the outer membrane of mitochondria and release caspase-activating proteins [87]. Some studies have shown cytochrome c release before collapse of the mitochondrial membrane potential [83] suggesting alternate control of the FT pore. Many, but not all, of the members of the Bd-2 family of proteins reside in the inner mitochondrial membrane, form ionic channels in hpid membranes and increase rates of proton extrusion in mitochondria [88] and thus may control the FT pore. The antiapoptotic and mitochondrial affects of Bd-2 are independent of caspase activity as they occur in the presence of caspase inhibitors and also in yeast that lack caspases [86]. 

Pan, M.H., Huang, Y.T., Ho, C.T., Chang, C.I., Hsu, PC., and Sun Pan, B. Indnction of apoptosis hy Meretrix lusoria throngh reactive oxygen species production, glutathione depletion, and caspase activation in human leukemia cells. Life Sci 79 1140-1152, 2006. 

Le DA, Wu Y, Huang Z, Matsushita K, Plesnila N, Augustinack JC, Hyman BT, Yuan J, Kuida K, Flavell RA, Moskowitz MA. Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation. Proc Natl Acad Sci USA. 2002 99 15188-15193... 

Shen, H.M., Zhang, Z., Zhang, Q.F., and Ong, C.N., Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol, 280, LI0-17, 2001. 

TMT poisoning leads to apopotic cell death including nuclear fragmentation, chromatin condensation, membrane blebbing, caspase activation, mitochondrial dysfunction, and production of reactive oxygen compounds [60,66-69]. 

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

Intrinsic system Apoptosis is initiated due to changes to the mitochondria during which the inner membrane becomes permeable to large molecules, probably as a result of a decrease in the membrane potential. This can result from intracellular damage (e.g. accumulation of Ca ions), lack of oxygen or fuel. This results in release of cytochrome c and other proteins from the mitochondria which stimulate apoptosis. In fact, these apoptotic proteins plus cytochrome c form a complex, the apoptosome, which activates an initiator caspase. 

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