scholarly journals Control of cell death/survival balance by the MET dependence receptor

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Leslie Duplaquet ◽  
Catherine Leroy ◽  
Audrey Vinchent ◽  
Sonia Paget ◽  
Jonathan Lefebvre ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase Cleavage ◽  
Physiological Importance ◽  
Signaling Mechanisms ◽  
Caspase Cleavage Site ◽  
Dependence Receptors ◽  
Dependence Receptor ◽  
Shed Light ◽  
Membrane Region

Control of cell death/survival balance is an important feature to maintain tissue homeostasis. Dependence receptors are able to induce either survival or cell death in presence or absence of their ligand, respectively. However, their precise mechanism of action and their physiological importance are still elusive for most of them including the MET receptor. We evidence that pro-apoptotic fragment generated by caspase cleavage of MET localizes to the mitochondria-associated membrane region. This fragment triggers a calcium transfer from endoplasmic reticulum to mitochondria, which is instrumental for the apoptotic action of the receptor. Knock-in mice bearing a mutation of MET caspase cleavage site highlighted that p40MET production is important for FAS-driven hepatocyte apoptosis, and demonstrate that MET acts as a dependence receptor in vivo. Our data shed light on new signaling mechanisms for dependence receptors’ control of cell survival/death balance, which may offer new clues for the pathophysiology of epithelial structures.

scholarly journals Failure of Poly(ADP-Ribose) Polymerase Cleavage by Caspases Leads to Induction of Necrosis and Enhanced Apoptosis

1999 ◽  
Vol 19 (7) ◽  
pp. 5124-5133 ◽  
Author(s):  
Zdenko Herceg ◽  
Zhao-Qi Wang
Keyword(s):  
Cell Death ◽  
Parp Inhibitor ◽  
Cell Types ◽  
Parp Cleavage ◽  
Dna Breaks ◽  
Necrosis Factor Alpha ◽  
Caspase Cleavage ◽  
Protein Resistant

ABSTRACT Activation of poly(ADP-ribose) polymerase (PARP) by DNA breaks catalyzes poly(ADP-ribosyl)ation and results in depletion of NAD+ and ATP, which is thought to induce necrosis. Proteolytic cleavage of PARP by caspases is a hallmark of apoptosis. To investigate whether PARP cleavage plays a role in apoptosis and in the decision of cells to undergo apoptosis or necrosis, we introduced a point mutation into the cleavage site (DEVD) of PARP that renders the protein resistant to caspase cleavage in vitro and in vivo. Here, we show that after treatment with tumor necrosis factor alpha, fibroblasts expressing this caspase-resistant PARP exhibited an accelerated cell death. This enhanced cell death is attributable to the induction of necrosis and an increased apoptosis and was coupled with depletion of NAD+ and ATP that occurred only in cells expressing caspase-resistant PARP. The PARP inhibitor 3-aminobenzamide prevented the NAD+ drop and concomitantly inhibited necrosis and the elevated apoptosis. These data indicate that this accelerated cell death is due to NAD+ depletion, a mechanism known to kill various cell types, caused by activation of uncleaved PARP after DNA fragmentation. The present study demonstrates that PARP cleavage prevents induction of necrosis during apoptosis and ensures appropriate execution of caspase-mediated programmed cell death.

The role of the N-terminal caspase cleavage site in the nucleoprotein of influenza A virus in vitro and in vivo

2007 ◽  
Vol 153 (3) ◽  
pp. 427-434 ◽  
Author(s):  
A. S. Lipatov ◽  
H.-L. Yen ◽  
R. Salomon ◽  
H. Ozaki ◽  
E. Hoffmann ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Cleavage Site ◽  
Influenza A ◽  
Caspase Cleavage ◽  
Caspase Cleavage Site

Caspase-independent cell death in AML: caspase inhibition in vitro with pan-caspase inhibitors or in vivo by XIAP or Survivin does not affect cell survival or prognosis

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4179-4186 ◽  
Author(s):  
Bing Z. Carter ◽  
Steven M. Kornblau ◽  
Twee Tsao ◽  
Rui-Yu Wang ◽  
Wendy D. Schober ◽  
...  
Keyword(s):  
Cell Death ◽  
Adenosine Diphosphate ◽  
Prognostic Impact ◽  
Caspase Cleavage ◽  
Caspase Inhibition ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor ◽  
The Impact

Abstract Survivin and XIAP, members of the protein family known as the inhibitors of apoptosis, interfere with the activation of caspases, called the “cell death executioners.” We examined Survivin (n = 116) and XIAP (n = 172) expression in primary acute myeloid leukemia (AML) blasts and assessed the impact of their expression on prognosis. They were detected in all samples analyzed. However, no correlation was observed with cytogenetics, remission attainment, or overall survival of patients with AML. To investigate the importance of caspases in chemotherapy-induced apoptosis in AML, we treated OCI-AML3 cells with Ara-C, doxorubicin, vincristine, and paclitaxel, which induced caspase cleavage and apoptosis. Blocking of caspase activation by pan-caspase inhibitor abolished poly(adenosine diphosphate [ADP]-ribose) polymerase cleavage and DNA fragmentation but did not prevent chemotherapy-induced cell death and did not inhibit, or only partially inhibited, mitochondrial release of cytochrome c, Smac, apoptosis-inducing factor (AIF), or loss of mitochondrial membrane potential. Caspase inhibition also did not protect AML blasts from chemotherapy-induced cell death in vitro. These results suggest that expression levels of Survivin or XIAP have no prognostic impact in AML patients. Although anticancer drugs induced caspase cleavage and apoptosis, cell killing was caspase independent. This may partially explain the lack of prognostic impact of XIAP and Survivin and may suggest caspase-independent mechanisms of cell death in AML. (Blood. 2003;102:4179-4186)

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

scholarly journals Identification of a novel caspase cleavage site in huntingtin that regulates mutant huntingtin clearance

2018 ◽  
Vol 33 (3) ◽  
pp. 3190-3197 ◽  
Author(s):  
Dale D. O. Martin ◽  
Mandi E. Schmidt ◽  
Yen T. Nguyen ◽  
Nikola Lazic ◽  
Michael R. Hayden
Keyword(s):  
Cleavage Site ◽  
Mutant Huntingtin ◽  
Caspase Cleavage ◽  
Caspase Cleavage Site

scholarly journals Attacins: A Promising Class of Insect Antimicrobial Peptides

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Francesco Buonocore ◽  
Anna Maria Fausto ◽  
Giulia Della Pelle ◽  
Tomislav Roncevic ◽  
Marco Gerdol ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Effect ◽  
Short Review ◽  
Microbial Pathogens ◽  
Special Focus ◽  
Gram Negative Bacteria ◽  
Physiological Importance ◽  
Related Proteins ◽  
Large Repertoire

Insects produce a large repertoire of antimicrobial peptides (AMPs) as the first line of defense against bacteria, viruses, fungi or parasites. These peptides are produced from a large precursor that contains a signal domain, which is cleaved in vivo to produce the mature protein with antimicrobial activity. At present, AMPs from insects include several families which can be classified as cecropins, ponericins, defensins, lebocins, drosocin, Metchnikowin, gloverins, diptericins and attacins according to their structure and/or function. This short review is focused on attacins, a class of glycine-rich peptides/proteins that have been first discovered in the cecropia moth (Hyalophora cecropia). They are a rather heterogeneous group of immunity-related proteins that exhibit an antimicrobial effect mainly against Gram-negative bacteria. Here, we discuss different attacin and attacin-like AMPs that have been discovered so far and analyze their structure and phylogeny. Special focus is given to the physiological importance and mechanism of action of attacins against microbial pathogens together with their potential pharmacological applications, emphasizing their roles as antimicrobials.

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