Death receptor-induced apoptotic and necrotic cell death: differential role of caspases and mitochondria

Abstract

In L929sAhFas cells, tumor necrosis factor (TNF) leads to necrotic cell death, whereas agonistic anti-Fas antibodies elicit apoptotic cell death. Apoptosis, but not necrosis, is correlated with a rapid externalization of phosphatidylserine and the appearance of a hypoploid population. During necrosis no cytosolic and organelle-associated active caspase-3 and -7 fragments are detectable. The necrotic process does not involve proteolytic generation of truncated Bid; moreover, no mitochondrial release of cytochrome c is observed. Bcl-2 overexpression slows down the onset of necrotic cell death. In the case of apoptosis, active caspases are released to the culture supernatant, coinciding with the release of lactate dehydrogenase. Following necrosis, mainly unprocessed forms of caspases are released. Both TNFinduced necrosis and necrosis induced by anti-Fas in the presence of the caspase inhibitor benzyloxycarbonyl-Val-AlaAsp(OMe)-fluoromethylketone are prevented by the serine protease inhibitor N-tosyl-L-phenylalanine chloromethylketone and the oxygen radical scavenger butylated hydroxyanisole, while Fas-induced apoptosis is not affected. Cell Death and Differentiation (2001) 8, 829 ± 840.

Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells

“…Despite having apoptotic signals, cells would still undergo necrosis if the ATP levels are low. Presence of mini-MUC4 by itself might be providing survival signals and preventing the apoptosis; however, due to lack of survival signals in the absence of mini-MUC4 and due to reduced levels of ATP in the vector containing cells, these cells might undergo necrosis (Bernardi et al, 1999;Denecker et al, 2001). The mechanism and the pathways involved in this phenomenon still need to be determined.…”

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

“…One recent study shows that the apoptotic pathway is associated with massive release of activated caspases into the media, whereas in necrotic cells only inactive procaspases were detectable (Denecker et al 2001). In the cochlea, apoptosis and necrosis appear to be intertwined in their own unique fashion in a process that is only now beginning to be uncovered.…”

Autophagy, Apoptosis, Mitoptosis and Necrosis: Interdependence Between Those Pathways and Effects on Cancer

“…controls activation of PLA (polylactic acid), calpains and nitric oxide synthase (NOS), which induce a series of events leading to necrotic cell death. Mitochondria contribute to necrosis by excessive reactive oxygen species (ROS) formation, mitochondrial permeability transition, and ATP depletion due to mitochondrial dysfunction (Denecker et al 2001). …”

“…This indicates the importance of RIPK1, -3 and PARP-1 for the induction of necrosis. Concomitantly, the inhibition of caspases leads to enhanced and accelerated ROS formation (Denecker et al 2001;Los et al 2001Los et al , 2002.…”