Growth suppression and apoptosis-like cell death in Microcystis aeruginosa by H2O2: A new insight into extracellular and intracellular damage pathways

Salicylic acid (SA) is well known hormonal molecule involved in cell death regulation. In response to a broad range of environmental factors (e.g., high light, UV, pathogens attack), plants accumulate SA, which participates in cell death induction and spread in some foliar cells. LESION SIMULATING DISEASE 1 (LSD1) is one of the best-known cell death regulators in Arabidopsis thaliana. The lsd1 mutant, lacking functional LSD1 protein, accumulates SA and is conditionally susceptible to many biotic and abiotic stresses. In order to get more insight into the role of LSD1-dependent regulation of SA accumulation during cell death, we crossed the lsd1 with the sid2 mutant, caring mutation in ISOCHORISMATE SYNTHASE 1(ICS1) gene and having deregulated SA synthesis, and with plants expressing the bacterial nahG gene and thus decomposing SA to catechol. In response to UV A+B irradiation, the lsd1 mutant exhibited clear cell death phenotype, which was reversed in lsd1/sid2 and lsd1/NahG plants. The expression of PR-genes and the H2O2 content in UV-treated lsd1 were significantly higher when compared with the wild type. In contrast, lsd1/sid2 and lsd1/NahG plants demonstrated comparability with the wild-type level of PR-genes expression and H2O2. Our results demonstrate that SA accumulation is crucial for triggering cell death in lsd1, while the reduction of excessive SA accumulation may lead to a greater tolerance toward abiotic stress.

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Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8

Nature Communications ◽

10.1038/s41467-020-20319-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Qin Gong ◽

Kim Robinson ◽

Chenrui Xu ◽

Phuong Thao Huynh ◽

Kelvin Han Chung Chong ◽

...

Keyword(s):

Cell Death ◽

Inner Core ◽

Inflammatory Diseases ◽

Structural Features ◽

Structural Basis ◽

Cultured Human Cells ◽

Structural Insight ◽

Sensor Proteins ◽

Insight Into

AbstractNod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIINDUPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells—a process that is greatly enhanced by NLRP1-FIINDUPA which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.

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prICE: a downstream target for ceramide-induced apoptosis and for the inhibitory action of Bcl-2

Biochemical Journal ◽

10.1042/bj3160025 ◽

1996 ◽

Vol 316 (1) ◽

pp. 25-28 ◽

Cited By ~ 153

Author(s):

Miriam J. SMYTH ◽

David K. PERRY ◽

Jiandi ZHANG ◽

Guy G. POIRIER ◽

Yusuf A. HANNUN ◽

...

Keyword(s):

Cell Death ◽

Inhibitory Action ◽

Second Messenger ◽

The Novel ◽

Over Expression ◽

Downstream Target ◽

Induced Apoptosis ◽

Insight Into

The novel lipid second messenger, ceramide, specifically induced poly(ADP-ribose) polymerase cleavage through activation of the protease prICE. Over-expression of Bcl-2 inhibited ceramide-induced poly(ADP-ribose) polymerase proteolysis and protected cells from ceramide-induced death. These data provide the first insight into the mechanism by which ceramide mediates apoptosis and suggest a mechanism by which Bcl-2 protects from cell death.

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IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos

Blood ◽

10.1182/blood-2018-05-850727 ◽

2018 ◽

Vol 132 (20) ◽

pp. 2166-2178 ◽

Cited By ~ 18

Author(s):

Pasquale L. Fedele ◽

Simon N. Willis ◽

Yang Liao ◽

Michael S. Low ◽

Jai Rautela ◽

...

Keyword(s):

Cell Death ◽

Regulatory Networks ◽

Nk Cell ◽

Surface Expression ◽

Nucleosome Remodeling ◽

Interferon Stimulated Genes ◽

Cd38 Expression ◽

Cycle Arrest ◽

Transcriptional Changes ◽

Insight Into

Abstract Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream gene regulatory networks. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment. This was not dependent on reduction of the IRF4-MYC “axis,” as neither protein was consistently downregulated, despite cell death occurring, and overexpression of either factor failed to rescue for Ikaros loss. Importantly, Ikaros and Aiolos repress the expression of interferon-stimulated genes (ISGs), including CD38, and their loss led to the activation of an interferon-like response, contributing to MM cell death. Ikaros/Aiolos repressed CD38 expression through interaction with the nucleosome remodeling and deacetylase complex in MM. IMiD-induced loss of Ikaros or treatment with interferon resulted in an upregulation of CD38 surface expression on MM cells, priming for daratumumab-induced NK cell-mediated antibody-dependent cellular cytotoxicity. These results give further insight into the mechanism of action of the IMiDs and provide mechanistic rationale for combination with anti-CD38 monoclonal antibodies.

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Role of two metacaspases in development and pathogenicity of the Rice Blast fungus, Magnaporthe oryzae

10.1101/2020.12.10.420794 ◽

2020 ◽

Author(s):

Jessie Fernandez ◽

Victor Lopez ◽

Lisa Kinch ◽

Mariel A. Pfeifer ◽

Hillery Gray ◽

...

Keyword(s):

Cell Death ◽

Food Security ◽

Life Cycle ◽

Magnaporthe Oryzae ◽

Rice Blast ◽

Rice Blast Disease ◽

Blast Disease ◽

Complex Life Cycle ◽

Insight Into

ABSTRACTRice blast disease caused by Magnaporthe oryzae is a devastating disease of cultivated rice worldwide. Infections by this fungus lead to a significant reduction in rice yields and threats to food security. To gain better insight into growth and cell death in M. oryzae during infection, we characterized two predicted M. oryzae metacaspase proteins, MoMca1 and MoMca2. These proteins appear to be functionally redundant and are able to complement the yeast Yca1 homologue. Biochemical analysis revealed that M. oryzae metacaspases exhibited Ca2+ dependent caspase activity in vitro. Deletion of both MoMca1 and MoMca2 in M. oryzae resulted in reduced sporulation, delay in conidial germination and attenuation of disease severity. In addition, the double ΔMomca1mca2 mutant strain showed increased radial growth in the presence of oxidative stress. Interestingly, the ΔMomca1mca2 strain showed an increase accumulation of insoluble aggregates compared to the wild-type strain during vegetative growth. Our findings suggest that MoMca1 and MoMca2 promote the clearance of insoluble aggregates in M. oryzae, demonstrating the important role these metacaspases have in fungal protein homeostasis. Furthermore, these metacaspase proteins may play additional roles, like in regulating stress responses, that would help maintain the fitness of fungal cells required for host infection.IMPORTANCEMagnaporthe oryzae causes rice blast disease that threatens global food security by resulting in the severe loss of rice production every year. A tightly regulated life cycle allows M. oryzae to disarm the host plant immune system during its biotrophic stage before triggering plant cell death in its necrotrophic stage. The ways M. oryzae navigates its complex life cycle remains unclear. This work characterizes two metacaspase proteins with peptidase activity in M. oryzae that are shown to be involved in the regulation of fungal growth and development prior to infection by potentially helping maintain fungal fitness. This study provides new insight into the role of metacaspase proteins in filamentous fungi by illustrating the delays in M. oryzae morphogenesis in the absence of these proteins. Understanding the mechanisms by which M. oryzae morphology and development promote its devastating pathogenicity may lead to the emergence of proper methods for disease control.

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Insight into the Double-Edged Role of Ferroptosis in Disease

Biomolecules ◽

10.3390/biom11121790 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1790

Author(s):

Lei Zhang ◽

Ruohan Jia ◽

Huizhen Li ◽

Huarun Yu ◽

Keke Ren ◽

...

Keyword(s):

Cell Death ◽

Digestive System ◽

Kidney Injury ◽

Oxygen Species ◽

Disease Treatment ◽

The Relationship ◽

Insight Into ◽

New Strategies ◽

Research Hotspots

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.

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Induction of programmed cell death in human hematopoietic cell lines by fibronectin via its interaction with very late antigen 5.

Journal of Experimental Medicine ◽

10.1084/jem.179.6.1757 ◽

1994 ◽

Vol 179 (6) ◽

pp. 1757-1766 ◽

Cited By ~ 67

Author(s):

H Sugahara ◽

Y Kanakura ◽

T Furitsu ◽

K Ishihara ◽

K Oritani ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cell Lines ◽

Growth Suppression ◽

Hematopoietic Cell ◽

Leukemia Cell Line ◽

Gm Csf ◽

Late Antigen ◽

Antigen 5 ◽

Hematopoietic Cell Lines

Extracellular matrix (ECM) molecules such as fibronectin (FN), collagens, and laminin have important roles in hematopoiesis. However, little is known about the precise mechanisms by which ECM molecules regulate proliferation of human hematopoietic progenitor cells. In this study, we have investigated the effects of ECM molecules, particularly of FN, on the proliferation of a myeloid leukemia cell line, M07E, which proliferates in response to either human granulocyte/macrophage colony-stimulating factor (GM-CSF) or stem cell factor (SCF). The [3H]thymidine incorporation and cell enumeration assays showed that FN strikingly inhibited GM-CSF- or SCF-induced proliferation of M07E cells in a dose-dependent manner, whereas little or no inhibition was induced by collagen types I and IV. The growth suppression of M07E cells was not due to the inhibitory effect of FN on ligand binding or very early events in the signal transduction pathways from the GM-CSF or SCF receptors. DNA content analysis using flow cytometry after staining with propidium iodide revealed that the treatment of M07E cells with FN did not block the entry of the cells into the cell cycle after stimulation with GM-CSF or SCF, whereas the treatment resulted in the appearance of subdiploid peak. Furthermore, FN was found to induce oligonucleosomal DNA fragmentation and chromatin condensation in the cells even in the presence of GM-CSF or SCF, suggesting the involvement of programmed cell death (apoptosis) in the FN-induced growth suppression. The growth suppression or apoptosis induced by FN was rescued by the addition of either anti-FN antibody, anti-very late antigen 5 monoclonal antibody (anti-VLA5 mAb), or GRGDSP peptide, but not by that of anti-VLA4 mAb or GRGESP peptide, suggesting that the FN effects on M07E cells were mediated through VLA5. In addition, the FN-induced apoptosis was detectable in VLA5-positive human hematopoietic cell lines other than M07E cells, but not in any of the VLA5-negative cell lines. These results suggest that FN is capable of inducing apoptosis via its interaction with VLA5, and also raise the possibility that the FN-VLA5 interaction may contribute, at least in part, to negative regulation of hematopoiesis.

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The growth suppression effects of UV-C irradiation on Microcystis aeruginosa and Chlorella vulgaris under solo-culture and co-culture conditions in reclaimed water

The Science of The Total Environment ◽

10.1016/j.scitotenv.2019.136374 ◽

2020 ◽

Vol 713 ◽

pp. 136374 ◽

Cited By ~ 1

Author(s):

Shang Li ◽

Guo-Hua Dao ◽

Yi Tao ◽

Ji Zhou ◽

Hai-Sha Jiang ◽

...

Keyword(s):

Microcystis Aeruginosa ◽

Chlorella Vulgaris ◽

Reclaimed Water ◽

Culture Conditions ◽

Growth Suppression ◽

Uv C ◽

Suppression Effects

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Regulation of Mitochondrial Ca2+ Uptake

Annual Review of Physiology ◽

10.1146/annurev-physiol-031920-092419 ◽

2020 ◽

Vol 83 (1) ◽

Author(s):

Elizabeth Murphy ◽

Charles Steenbergen

Keyword(s):

Cell Death ◽

Genetic Alterations ◽

Annual Review ◽

Publication Date ◽

Mitochondrial Matrix ◽

Atp Production ◽

The Past ◽

Specific Manner ◽

Insight Into ◽

Disease Specific

Mitochondria are responsible for ATP production but are also known as regulators of cell death, and mitochondrial matrix Ca2+ is a key modulator of both ATP production and cell death. Although mitochondrial Ca2+ uptake and efflux have been studied for over 50 years, it is only in the past decade that the proteins responsible for mitochondrial Ca2+ uptake and efflux have been identified. The identification of the mitochondrial Ca2+ uniporter (MCU) led to an explosion of studies identifying regulators of the MCU. The levels of these regulators vary in a tissue- and disease-specific manner, providing new insight into how mitochondrial Ca2+ is regulated. This review focuses on the proteins responsible for mitochondrial transport and what we have learned from mouse studies with genetic alterations in these proteins. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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