Apoptosis necrosis switch

Nicotera P, Melino G. Regulation of the apoptosis-necrosis switch. Oncogene 2004 23 2757-2765. 

McCarthy NJ, et al. Inhibition of Ced-3/ICE-related proteases does not prevent ceU death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak. J. Cell Biol. 1997 136 215-227. Hirsch T, et al. The apoptosis-necrosis paradox. Apoptogenic proteases activated after mitochondrial permeability transition determine the mode of ceU death. Oncogene 1997 15 1573-1581. Leist M, et al. Inhibition of mitochondrial ATP generation by nitric oxide switches apoptosis to necrosis. Exp. Cell Res. 1999 249 396-403. 

Lemaire, C., Andreau, K., Souvarmavong, V. and Adam, A. (1998) Inhibition of caspase activity induces a switch from apoptosis to necrosis. FEBS Lett., 425, 266-270. 

Nicotera P, Leist M, Ferrando-May E. Intracellular ATP, a switch in the decision between apoptosis and necrosis. Toxicol Lett 1998 102-103 139-142. 

LeDoux SP, Driggers WJ, Hollensworth BS, Wilson GL (1999) Repair of alkylation and oxidative damage in mitochondrial DNA. Mutation Res 434 149-159 Leist M, Single B, Castoldi AF, Kiihnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration a switch in the decision between apoptosis and necrosis. J Exp Med 185 1481-1486... 

Table 2. PARP activation switches apoptosis to necrosis in DNA damaged cells ... 

Los M, Mozoluk M, Ferrari D et al. Activation and caspase-mediated inhibition of PARP A molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell 2002 13(3) 978-988. 

It is interesting to note that 6 h after intense NMDA exposure, DPQ-pretreated cells exhibited a significant increase in caspase-3-like activity that was associated with an increase in the number of apoptotic cells. These data surest that, as a result of PARP-1 inhibition and the subsequent recovery of ATP levels, there could be a shift in the type of cell death, allowing some cells that would have otherwise died by necrosis to die by apoptosis. In accordance with this view, previous studies have reported that the maintenance of cellular energy levels induced by PARP-1 inhibition after injury permits caspase activation and switches the type of cell death from necrosis to apoptosis. The recovery of energr levels induced by PARP-1 inhibition can also allow the survival of some cells destined to die by apoptosis, as reported in PC 12 cells exposed to oxidative damage. ... 

Inhibition of cell death signaling pathways can initiate a ceU to re-wire its cell death program from apoptosis to necrosis [549] through a molecular switch. Earlier studies put forward ATP [550] or caspases [551] as the mediator. Depletion of ATP would favor necrosis, which can be explained by energy demands during... 

Necrosis occurrence is dependent on the concentration of Cd applied and the levels of ATP appear to be very important. The scenario for cell death switch in Cd Ntreated cells is somewhat more complicated but ATP, GSH status and peroxide accumulation are all involved [552]. In addition, metallothionein-3 (MT-3) seems to have an important role in controlling the form of ceU death. In kidney cells with low MT-3 expression, Cd " causes apoptosis but MT-3 overexpressing cells show necrosis by Cd [554]. The mechanism by which MT-3 predisposes cells to necrotic ceU death was not investigated but previous studies report a non-canonical neuronal ceU growth inhibitory activity of MT-3, which may be related to its necrosis inducing abilities. 

Fabris, C., Valduga, G., Miotto, G., Borsetto, L., Jori, G., Garbisa, S., and Reddi, E., Photosensitization with zinc (11) phthalocyanine as a switch in the decision between apoptosis and necrosis. Cancer Res., 61, 7495, 2001. 

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