scholarly journals An Overlap between the Control of Programmed Cell Death in Bacillus anthracis and Sporulation

2009 ◽  
Vol 191 (13) ◽  
pp. 4103-4110 ◽  
Author(s):  
Lakshmi Chandramohan ◽  
Jong-Sam Ahn ◽  
Keith E. Weaver ◽  
Kenneth W. Bayles
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Stationary Phase ◽  
Bacillus Anthracis ◽  
Bacterial Species ◽  
Control Cell ◽  
Dependent Manner ◽  
Positive Role ◽  
Stationary Phase Survival ◽  
Eukaryotic Organisms

ABSTRACT The Staphylococcus aureus cid and lrg operons have been shown to control cell death and lysis in a manner thought to be analogous to programmed cell death (apoptosis) in eukaryotic organisms. Although orthologous operons are present in a wide variety of bacterial species, members of the Bacillus cereus group are unique in that they have a total of four cid-/lrg-like operons. Two of these operons are similar to the S. aureus cid and lrg operons, while the other two (designated clhAB 1 and clhAB 2) are unique to this group. In the present study, the functions and regulation of these loci were examined. Interestingly, the Bacillus anthracis lrgAB mutant displayed decreased stationary-phase survival, whereas the clhAB 2 mutant exhibited increased stationary-phase survival compared to the parental and complementation strains. However, neither mutation had a dramatic effect on murein hydrolase activity or autolysis. Furthermore, a quantitative analysis of the sporulation efficiency revealed that both mutants formed fewer spores than did the parental strain. Similar to S. aureus, B. anthracis lrgAB transcription was shown to be induced by gramicidin and CCCP, agents known to dissipate the proton motive force, in a lytSR-dependent manner. Northern blot analyses also demonstrated a positive role for lytSR in the clhAB 2 transcription. Taken together, the results of the present study demonstrate that B. anthracis lrgAB and clhAB 2 play important roles in the control of cell death and lysis and reveal a previously unrecognized role of this system in sporulation.

scholarly journals Recent Advancements in Toxin and Antitoxin Systems Involved in Bacterial Programmed Cell Death

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Ming-xi Hu ◽  
Xiao Zhang ◽  
Er-li Li ◽  
Yong-Jun Feng
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Significant Role ◽  
Environmental Stresses ◽  
Biological Processes ◽  
Eukaryotic Organisms ◽  
Evolutionary Perspectives

Programmed cell death (PCD) systems have been extensively studied for their significant role in a variety of biological processes in eukaryotic organisms. Recently, more and more researches have revealed the existence of similar systems employed by bacteria in response to various environmental stresses. This paper summarized the recent researching advancements in toxin/antitoxin systems located on plasmids or chromosomes and their regulatory roles in bacterial PCD. The most studied yet disputedmazEFsystem was discussed in depth, and possible roles and status of such a special bacterial death and TA systems were also reviewed from the ecological and evolutionary perspectives.

scholarly journals An Endopolygalacturonase from Sclerotinia sclerotiorum Induces Calcium-Mediated Signaling and Programmed Cell Death in Soybean Cells

2005 ◽  
Vol 18 (8) ◽  
pp. 849-855 ◽  
Author(s):  
Anna Zuppini ◽  
Lorella Navazio ◽  
Luca Sella ◽  
Carala Castiglioni ◽  
Francesco Favaron ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Sclerotinia Sclerotiorum ◽  
Phase 1 ◽  
Control Cell ◽  
Cell Contact ◽  
Cytochrome C Release ◽  
Soybean Seedlings ◽  
Polygalacturonase Inhibiting Protein

A basic endopolygalacturonase (PG) isoform, produced early by Sclerotinia sclerotiorum when infecting soybean seedlings, was used to examine the signaling role of the enzyme in aequorin-expressing soybean cells. A cytosolic Ca2+ elevation was induced, with a rapid increase (phase 1) and a very slow decrease (phase 2) of Ca2+ concentration, indicating the involvement of Ca2+ ions in PG signaling. Within 1 h of PG-cell contact a remarkable level of cell death was recorded, significantly higher than the control cell culture turnover. The observed morphological and biochemical changes were indicative of the activation of programmed cell death; in particular, cytochrome c release in the cytoplasm and activation of both caspase 9-like and caspase 3-like proteases were found. When a polygalacturonase-inhibiting protein (PGIP) and the PG were simultaneously applied to cells, both the Ca2+ increase and cell death were annulled. The possible roles of prolonged sustained cytosolic Ca2+ concentrations in inducing cell death and of the PG-PGIP interaction in preventing PG signaling are discussed.

Cancer and cell death

2019 ◽  
pp. 196-208
Author(s):  
Jessica Bullenkamp ◽  
Mahvash Tavassoli
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tumour Growth ◽  
Cellular Proliferation ◽  
Control Cell ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Constant Number ◽  
Normal Tissues ◽  
Multicellular Organisms

Programmed cell death is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. Regulated programmed cell death is one of the mechanisms by which multicellular organisms limit the growth and replication of cells. Cell death is essential to control cell growth and tissue homeostasis; it occurs in normal tissues to allow the removal of damaged cells or to maintain a constant number of cells in regenerating tissues and plays an important part in embryogenesis. In an average human adult 50–70 billion cells undergo programmed cell death every day. The abundance of literature suggests that defects in programmed cell death play a crucial role in carcinogenesis. The genetic alterations in the cancer cell not only lead to increased cellular proliferation, as discussed in other chapters of this book, but also lead to loss of programmed cell death, thus increasing tumour growth. Despite being part of the problem, cell death plays an important role in the treatment of cancer as it is an important target of many treatment strategies. Unquestionably, apoptosis is the best-characterized and the most evolutionary conserved form of programmed cell death. Recently, many studies have demonstrated the existence of several other forms of programmed cell death including autophagy, necroptosis, and pyroptosis. In this chapter we discuss several regulated forms of cell death; we outline what we know about their mechanisms and how we can exploit this knowledge to reactivate programmed cell death in tumour cells for the treatment of cancer.

scholarly journals MicroRNA-223-3p Protect Against Radiation-Induced Cardiac Toxicity by Alleviating Myocardial Oxidative Stress and Programmed Cell Death via Targeting the AMPK Pathway

2022 ◽  
Vol 9 ◽  
Author(s):  
Dao-ming Zhang ◽  
Jun-jian Deng ◽  
Yao-gui Wu ◽  
Tian Tang ◽  
Lin Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Myocardial Injury ◽  
Adenosine Monophosphate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Compound C ◽  
Myocardial Oxidative Stress ◽  
Radiation Induced

Objectives: Radiotherapy improves the survival rate of cancer patients, yet it also involves some inevitable complications. Radiation-induced heart disease (RIHD) is one of the most serious complications, especially the radiotherapy of thoracic tumors, which is characterized by cardiac oxidative stress disorder and programmed cell death. At present, there is no effective treatment strategy for RIHD; in addition, it cannot be reversed when it progresses. This study aims to explore the role and potential mechanism of microRNA-223-3p (miR-223-3p) in RIHD.Methods: Mice were injected with miR-223-3p mimic, inhibitor, or their respective controls in the tail vein and received a single dose of 20 Gy whole-heart irradiation (WHI) for 16 weeks after 3 days to construct a RIHD mouse model. To inhibit adenosine monophosphate activated protein kinase (AMPK) or phosphodiesterase 4D (PDE4D), compound C (CompC) and AAV9-shPDE4D were used.Results: WHI treatment significantly inhibited the expression of miR-223-3p in the hearts; furthermore, the levels of miR-223-3p decreased in a radiation time-dependent manner. miR-223-3p mimic significantly relieved, while miR-223-3p inhibitor aggravated apoptosis, oxidative damage, and cardiac dysfunction in RIHD mice. In addition, we found that miR-223-3p mimic improves WHI-induced myocardial injury by activating AMPK and that the inhibition of AMPK by CompC completely blocks these protective effects of miR-223-3p mimic. Further studies found that miR-223-3p lowers the protein levels of PDE4D and inhibiting PDE4D by AAV9-shPDE4D blocks the WHI-induced myocardial injury mediated by miR-223-3p inhibitor.Conclusion: miR-223-3p ameliorates WHI-induced RIHD through anti-oxidant and anti-programmed cell death mechanisms via activating AMPK by PDE4D regulation. miR-223-3p mimic exhibits potential value in the treatment of RIHD.

scholarly journals Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Mediated Autophagy in Human Granulosa Cells as an Alternative of Programmed Cell Death

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3851-3860 ◽  
Author(s):  
Nicole Duerrschmidt ◽  
Olga Zabirnyk ◽  
Marcin Nowicki ◽  
Albert Ricken ◽  
Fayez A. Hmeidan ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Time Point

The LOX-1 receptor, identified on endothelial cells, mediates the uptake of oxidized low-density lipoprotein (oxLDL). The oxLDL-dependent LOX-1 activation causes endothelial cell apoptosis. We here investigated the presence of LOX-1 in granulosa cells from patients under in vitro fertilization therapy. We were interested in the oxLDL-dependent LOX-1 receptor biology, in particular in the induction of apoptosis. In the human ovary, LOX-1 was localized in regressing antral follicles. In granulosa cell cultures, oxLDL-induced mRNA expression of LOX-1 in a time- and dose-dependent manner. The LOX-1 inhibitors (anti-LOX-1 antibody and κ-carrageenan) abrogated the up-regulation of LOX-1. The oxLDL (100 μg/ml) treatment caused the autophagy form of programmed cell death: 1) reorganization of the actin cytoskeleton at the 6-h time point; 2) uptake of YO-PRO, a marker for the early step of programmed cell death, before propidium iodide staining to signify necrosis; 3) absence of apoptotic bodies and cleaved caspase-3; 4) abundant vacuole formation at the ultrastructural level; and 5) decrease of the autophagosome marker protein MAP LC3-I at the 6-h time point indicative of autophagosome formation. We conclude that follicular atresia is not under the exclusive control of apoptosis. The LOX-1-dependent autophagy represents an alternate form of programmed cell death. Obese women with high blood levels of oxLDL may display an increased rate of autophagic granulosa cell death.

scholarly journals Control of PD-L1 expression in CLL-cells by stromal triggering of the Notch-c-Myc-EZH2 oncogenic signaling axis

2021 ◽  
Vol 9 (4) ◽  
pp. e001889
Author(s):  
Martin Böttcher ◽  
Heiko Bruns ◽  
Simon Völkl ◽  
Junyan Lu ◽  
Elisavet Chartomatsidou ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Programmed Cell Death ◽  
Immune Escape ◽  
Ex Vivo ◽  
Lymphocytic Leukemia ◽  
Cell Contact ◽  
Dependent Manner ◽  
Signaling Axis

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Emerging data suggest that CLL-cells efficiently evade immunosurveillance. T-cell deficiencies in CLL include immuno(metabolic) exhaustion that is achieved by inhibitory molecules, with programmed cell death 1/programmed cell death ligand 1 (PD-L1) signaling emerging as a major underlying mechanism. Moreover, CLL-cells are characterized by a close and recurrent interaction with their stromal niches in the bone marrow and lymph nodes. Here, they receive nurturing signals within a well-protected environment. We could previously show that the interaction of CLL-cells with stroma leads to c-Myc activation that is followed by metabolic adaptations. Recent data indicate that c-Myc also controls expression of the immune checkpoint molecule PD-L1. Therefore, we sought out to determine the role of stromal contact for the CLL-cells’ PD-L1 expression and thus their immuno-evasive phenotype.To do so, we analyzed PD-L1 expression on CLL cell (subsets) in untreated patients and on healthy donor-derived B-cells. Impact of stromal contact on PD-L1 expression on CLL-cells and the underlying signaling pathways were assessed in well-established in vitro niche models. Ex vivo and in vitro findings were validated in the Eµ-TCL1 transgenic CLL mouse model.We found increased PD-L1 expression on CLL-cells as compared with B-cells that was further enhanced in a cell-to-cell contact-dependent manner by stromal cells. In fact, circulating recent stromal-niche emigrants displayed higher PD-L1 levels than long-time circulating CLL-cells. Using our in vitro niche model, we show that a novel Notch-c-Myc-enhancer of zeste homolog 2 (EZH2) signaling axis controls PD-L1 upregulation. Ultimately, elevated PD-L1 levels conferred increased resistance towards activated autologous T-cells.In summary, our findings support the notion that the CLL microenvironment contributes to immune escape variants. In addition, several targetable molecules (eg, Notch or EZH2) could be exploited in view of improving immune responses in patients with CLL, which warrants further in-depth investigation.

scholarly journals Discovery of Novel Small-Molecule Inhibitors of PD-1/PD-L1 Interaction via Structural Simplification Strategy

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3347
Author(s):  
Hongbo Zhang ◽  
Yu Xia ◽  
Chunqiu Yu ◽  
Huijie Du ◽  
Jinchang Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Life Time ◽  
Production Costs ◽  
Dependent Manner ◽  
Starting Point ◽  
Cell Inhibition ◽  
Structural Simplification

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.

scholarly journals The role of death domain proteins in host response upon SARS-CoV-2 infection: modulation of programmed cell death and translational applications

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikita V. Ivanisenko ◽  
Kamil Seyrek ◽  
Nikolay A. Kolchanov ◽  
Vladimir A. Ivanisenko ◽  
Inna N. Lavrik
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Death Domain ◽  
Global Public Health ◽  
Cell Death Pathways ◽  
Rapid Spread ◽  
Cell Signaling Networks

Abstract The current pandemic of novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) poses a significant global public health threat. While urgent regulatory measures in control of the rapid spread of this virus are essential, scientists around the world have quickly engaged in this battle by studying the molecular mechanisms and searching for effective therapeutic strategies against this deadly disease. At present, the exact mechanisms of programmed cell death upon SARS-CoV-2 infection remain to be elucidated, though there is increasing evidence suggesting that cell death pathways play a key role in SARS-CoV-2 infection. There are several types of programmed cell death, including apoptosis, pyroptosis, and necroptosis. These distinct programs are largely controlled by the proteins of the death domain (DD) superfamily, which play an important role in viral pathogenesis and host antiviral response. Many viruses have acquired the capability to subvert the program of cell death and evade the host immune response, mainly by virally encoded gene products that control cell signaling networks. In this mini-review, we will focus on SARS-CoV-2, and discuss the implication of restraining the DD-mediated signaling network to potentially suppress viral replication and reduce tissue damage.

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