BACKGROUND Necroptosis/programmed necrosis is initiated by a macro-molecular protein complex termed the necrosome. Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. TNFα is a prototypic inducer of necrosome activation, and it is widely believed that deubiquitination of RIP1 at the TNFR-1 signaling complex precedes transition of RIP1 into the cytoso...

Background: Necroptosis/programmed necrosis is initiated by a macro-molecular protein complex termed the necrosome. Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. TNFα is a prototypic inducer of necrosome activation, and it is widely believed that deubiquitination of RIP1 at the TNFR-1 signaling complex precedes transition of RIP1 into the cytos...

Although autophagy controls cell death and survival, underlying mechanisms are poorly understood, and it is unknown whether autophagy affects only whether or not cells die or also controls other aspects of programmed cell death. MAP3K7 is a tumor suppressor gene associated with poor disease-free survival in prostate cancer. Here, we report that Map3k7 deletion in mouse prostate cells sensitizes...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known apoptosis inducer and potential anticancer agent. When caspases inhibitors of proteins (IAPs) are inhibited, TRAIL induces necroptosis. Molecular mechanisms necroptosis rely on kinase activation, the formation necrosome complex, bringing together receptor-interacting protein kinases 1 3 (RIPK1, RIPK3), mixed lineage...

Regulated necrosis, termed necroptosis, is mediated by the kinase activity of RIPK1 and RIPK3. It has distinct cellular features that are different than apoptosis. Necroptosis can be triggered by extracellular stimuli known to activate inflammation and cell death and its intracellular signaling pathway involves necrosome formation and MLKL activation. Inhibition of necroptosis has been shown to...

BACKGROUND AND AIMS Severe acute pancreatitis is characterized by acinar cell death and inflammation. Necroptosis is an aggressive and pro-inflammatory mode of cell death that can be prevented by necrostatin-1 administration or RIP3 deletion. METHODS Mouse pancreatic acinar cells were incubated with supramaximally stimulating concentrations of caerulein or sub-micellar concentrations of TLCS ...

PURPOSE To investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS. EXPERIMENTAL DESIGN A model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation we...