Necrosis-like death can engage multiple pro-apoptotic Bcl-2 protein family members

Autor: Denise Tischner, Claudia Soratroi, Andreas Villunger, Claudia Manzl, Gerhard Krumschnabel
Rok vydání: 2012
Předmět:
Cancer Research
Programmed cell death
Indoles
Necroptosis
Clinical Biochemistry
Pharmaceutical Science
Apoptosis
Article
Receptors
Tumor Necrosis Factor
Amino Acid Chloromethyl Ketones
Cell Line
Mice
Necrosis
Autophagy
Animals
Autocrine signalling
Caspase
Adaptor Proteins
Signal Transducing
Pharmacology
biology
Tumor Necrosis Factor-alpha
Biochemistry (medical)
Imidazoles
Signal transducing adaptor protein
Intracellular Membranes
Cell Biology
Fibroblasts
Cell biology
Autocrine Communication
bcl-2 Homologous Antagonist-Killer Protein
Proto-Oncogene Proteins c-bcl-2
Mitochondrial permeability transition pore
Receptor-Interacting Protein Serine-Threonine Kinases
biology.protein
Tumor necrosis factor alpha
Poly(ADP-ribose) Polymerases
Lysosomes
BH3 Interacting Domain Death Agonist Protein
Cadmium
Zdroj: Apoptosis. 17:1197-1209
ISSN: 1573-675X
1360-8185
Popis: Necroptosis is a physiologically relevant mode of cell death with some well-described initiating events, but largely unknown executioners. Here we investigated necrostatin-1 (Nec-1) sensitive death elicited by different necroptosis stimuli in L929 mouse fibrosarcoma cells, mouse embryonic fibroblasts (MEF) and bone marrow-derived macrophages. We found that TNFα- or zVAD-induced necroptosis occurs independently of the recently implicated executioners Bmf or PARP-2, but can involve the Bcl-2 family proteins Bid and Bak. Furthermore, this type of necroptosis is associated with mitochondrial cytochrome c release and partly sensitive to cyclosporine A inhibition, suggesting a cross talk with the mitochondrial permeability transition pore. Necroptosis triggered by cadmium (Cd) exposure caused fully Nec-1-sensitive and caspase-independent death in L929 cells that was associated with autocrine TNFα-mediated feed-forward signalling. In MEF Cd-exposure elicited a mixed mode of cell death that was to some extent Nec-1-sensitive but also displayed features of apoptosis. It was partly dependent on Bmf and Bax/Bak, proteins typically considered to act pro-apoptotic, but ultimately insensitive to caspase inhibition. Overall, our study indicates that inducers of "extrinsic" and "intrinsic" necroptosis can both trigger TNF-receptor signalling. Further, necroptosis may depend on mitochondrial changes engaging proteins considered critical for MOMP during apoptosis that ultimately contribute to caspase-independent necrotic cell death.
Databáze: OpenAIRE
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