scholarly journals Bayonets over bombs: RIPK3 and MLKL restrict Listeria without triggering necroptosis

2019 ◽  
Vol 218 (6) ◽  
pp. 1773-1775 ◽  
Author(s):  
Ting Zhang ◽  
Siddharth Balachandran
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Epithelial Cells ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Membrane Rupture ◽  
Cell Biol ◽  
Bacterial Replication

RIPK3 induces necroptosis by phosphorylating MLKL, which then induces plasma membrane rupture and necrotic cell death. In this issue, Sai et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201810014) show that RIPK3-MLKL signaling in epithelial cells promotes Listeria clearance by directly suppressing cytosolic bacterial replication, without activating cell death.

scholarly journals Repurposing Cationic Amphiphilic Drugs and Derivatives to Engage Lysosomal Cell Death in Cancer Treatment

2020 ◽  
Vol 10 ◽  
Author(s):  
Michelle Hu ◽  
Kermit L. Carraway
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cellular Transformation ◽  
Therapeutic Window ◽  
Cell Populations ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Membrane Rupture ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

A major confounding issue in the successful treatment of cancer is the existence of tumor cell populations that resist therapeutic agents and regimens. While tremendous effort has gone into understanding the biochemical mechanisms underlying resistance to each traditional and targeted therapeutic, a broader approach to the problem may emerge from the recognition that existing anti-cancer agents elicit their cytotoxic effects almost exclusively through apoptosis. Considering the myriad mechanisms cancer cells employ to subvert apoptotic death, an attractive alternative approach would leverage programmed necrotic mechanisms to side-step therapeutic resistance to apoptosis-inducing agents. Lysosomal cell death (LCD) is a programmed necrotic cell death mechanism that is engaged upon the compromise of the limiting membrane of the lysosome, a process called lysosomal membrane permeabilization (LMP). The release of lysosomal components into the cytosol upon LMP triggers biochemical cascades that lead to plasma membrane rupture and necrotic cell death. Interestingly, the process of cellular transformation appears to render the limiting lysosomal membranes of tumor cells more fragile than non-transformed cells, offering a potential therapeutic window for drug development. Here we outline the concepts of LMP and LCD, and discuss strategies for the development of agents to engage these processes. Importantly, the potential exists for existing cationic amphiphilic drugs such as antidepressants, antibiotics, antiarrhythmics, and diuretics to be repurposed to engage LCD within therapy-resistant tumor cell populations.

scholarly journals Elisidepsin Interacts Directly with Glycosylceramides in the Plasma Membrane of Tumor Cells to Induce Necrotic Cell Death

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140782 ◽  
Author(s):  
José Manuel Molina-Guijarro ◽  
Carolina García ◽  
Álvaro Macías ◽  
Luis Francisco García-Fernández ◽  
Cristina Moreno ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
Necrotic Cell Death ◽  
Necrotic Cell

scholarly journals Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death

Cell Research ◽  
2013 ◽  
Vol 24 (1) ◽  
pp. 105-121 ◽  
Author(s):  
Xin Chen ◽  
Wenjuan Li ◽  
Junming Ren ◽  
Deli Huang ◽  
Wan-ting He ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Kinase Domain ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Mixed Lineage Kinase

scholarly journals Irvalec Inserts Into the Plasma Membrane Causing Rapid Loss of Integrity and Necrotic Cell Death in Tumor Cells

2012 ◽  
Vol 102 (3) ◽  
pp. 65a-66a
Author(s):  
Alvaro Macias ◽  
Jose M. Molina-Guijarro ◽  
Miren David ◽  
Cristina Moreno ◽  
de la Cruz Alicia ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Rapid Loss

scholarly journals Irvalec Inserts into the Plasma Membrane Causing Rapid Loss of Integrity and Necrotic Cell Death in Tumor Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e19042 ◽  
Author(s):  
José M. Molina-Guijarro ◽  
Álvaro Macías ◽  
Carolina García ◽  
Eva Muñoz ◽  
Luis F. García-Fernández ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Rapid Loss

Monocytic cell necrosis is mediated by potassium depletion and caspase-like proteases

1999 ◽  
Vol 276 (3) ◽  
pp. C717-C724 ◽  
Author(s):  
Michel Warny ◽  
Ciarán P. Kelly
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Cysteine Proteases ◽  
Morphological Features ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Monocytic Cell ◽  
Mitochondrial Permeability

Apoptosis is a physiological cell death that culminates in mitochondrial permeability transition and the activation of caspases, a family of cysteine proteases. Necrosis, in contrast, is a pathological cell death characterized by swelling of the cytoplasm and mitochondria and rapid plasma membrane disruption. Necrotic cell death has long been opposed to apoptosis, but it now appears that both pathways involve mitochondrial permeability transition, raising the question of what mediates necrotic cell death. In this study, we investigated mechanisms that promote necrosis induced by various stimuli ( Clostridium difficile toxins, Staphylococcus aureus alpha toxin, ouabain, nigericin) in THP-1 cells, a human monocytic cell line, and in monocytes. All stimuli induced typical features of necrosis and triggered protease-mediated release of interleukin-1β (IL-1β) and CD14 in both cell types. K+depletion was actively implicated in necrosis because substituting K+for Na+in the extracellular medium prevented morphological features of necrosis and IL-1β release. N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad-spectrum caspase inhibitor, prevented morphological features of necrosis, plasma membrane destruction, loss of mitochondrial membrane potential, IL-1β release, and CD14 shedding induced by all stimuli. Thus, in monocytic cells, necrosis is a cell death pathway mediated by passive K+efflux and activation of caspase-like proteases.

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