scholarly journals Widely Used Mutants of eiger, Encoding the Drosophila Tumor Necrosis Factor, Carry Additional Mutations in the NimrodC1 Phagocytosis Receptor

2020 ◽  
Vol 10 (12) ◽  
pp. 4707-4712
Author(s):  
Albana Kodra ◽  
Claire de la Cova ◽  
Abigail R. Gerhold ◽  
Laura A. Johnston
Keyword(s):  
Cell Death ◽  
Transmembrane Domain ◽  
Coding Region ◽  
Lymph Glands ◽  
Link Type ◽  
Cellular Debris ◽  
Wing Imaginal Discs ◽  
Wing Discs ◽  
Dying Cells ◽  
Cellular Components

The process of apoptosis in epithelia involves activation of caspases, delamination of cells, and degradation of cellular components. Corpses and cellular debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies of the Drosophila TNF, Eiger (Egr) and cell death in wing imaginal discs, the epithelial primordia of fly wings, we noticed that dying cells appeared to transiently accumulate in egr3 mutant wing discs, raising the possibility that their phagocytic engulfment by hemocytes was impaired. Further investigation revealed that lymph glands and circulating hemocytes from egr3 mutant larvae were completely devoid of NimC1 staining, a marker of phagocytic hemocytes. Genome sequencing uncovered mutations in the NimC1 coding region that are predicted to truncate the NimC1 protein before its transmembrane domain, and provide an explanation for the lack of NimC staining. The work that we report here demonstrates the presence of these NimC1 mutations in the widely used egr3 mutant, its sister allele, egr1, and its parental strain, Regg1GS9830. As the egr3 and egr1 alleles have been used in numerous studies of immunity and cell death, it may be advisable to re-evaluate their associated phenotypes.

scholarly journals Widely used mutants of eiger, encoding the Drosophila Tumor Necrosis factor, carry additional mutations in the NimrodC1 phagocytosis receptor

2020 ◽  
Author(s):  
Albana Kodra ◽  
Claire de la Cova ◽  
Abigail R. Gerhold ◽  
Laura A. Johnston
Keyword(s):  
Cell Death ◽  
Transmembrane Domain ◽  
Coding Region ◽  
Lymph Glands ◽  
Cellular Debris ◽  
Wing Imaginal Discs ◽  
Wing Discs ◽  
Dying Cells ◽  
Cellular Components ◽  
Necrosis Factor

AbstractThe process of apoptosis in epithelia involves activation of caspases, delamination of cells, and degradation of cellular components. Corpses and cellular debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies of the Drosophila TNF, Eiger (Egr) and cell death in wing imaginal discs, the epithelial primordia of fly wings, we noticed that dying cells persisted longer in egr3 mutant wing discs than in wild type discs, raising the possibility that their phagocytic engulfment by hemocytes was impaired. Further investigation revealed that lymph glands and circulating hemocytes from egr3 mutant larvae were completely devoid of NimC1 staining, a marker of phagocytic hemocytes. Genome sequencing uncovered mutations in the NimC1 coding region that are predicted to truncate the NimC1 protein before its transmembrane domain, and provide an explanation for the lack of NimC staining. The work that we report here demonstrates the presence of these NimC1 mutations in the widely used egr3 mutant, its sister allele, egr1, and its parental strain, Regg1GS9830. As the egr3 and egr1 alleles have been used in numerous studies of immunity and cell death, it may be advisable to re-evaluate their associated phenotypes.

scholarly journals Efferocytosis: An Interface between Apoptosis and Pathophysiology

2021 ◽  
Author(s):  
Bichandarkoil Jayaram Pratima ◽  
Namasivayam Nalini
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Immune System ◽  
Large Family ◽  
Pathogen Invasion ◽  
Molecular Pattern ◽  
Cellular Debris ◽  
Established Cell ◽  
Dying Cells ◽  
Shed Light

Several cell death modes, each with a unique feature and mode of inducing cell death have been established. Cell death occurring under physiological conditions is primarily caused by apoptosis, which is a non-inflammatory or silent process, whereas necroptosis or pyroptosis is triggered by pathogen invasion, which stimulates the immune system and induces inflammation. In physiology, clearing dead cells and associated cellular debris is necessary since billions of cells die during mammalian embryogenesis and every day in adult organisms. For degradation, dead cells produced by apoptosis are quickly engulfed by macrophages. This chapter will present a description of the phagocytosis of dead and dying cells, by a process known as efferocytosis. Macrophages and, to a lesser degree, other ‘professional’ phagocytes (such as monocytes and dendritic cells) and ‘non-professional’ phagocytes, such as epithelial cells, conduct efferocytosis. Recent discoveries have shed light on this mechanism and how it works to preserve homeostasis of tissue, repair of tissue and health of the organism. Caspases are a large family of proteases of cysteine acting in cascades. A cascade leading to activation of caspase 3 mediates apoptosis and is responsible for killing cells, hiring macrophages, and presenting a “eat me” signal(s). If macrophages do not effectively engulf apoptotic cells, they undergo secondary necrosis and release intracellular materials that reflect a molecular pattern associated with injury, which can lead to autoimmune diseases. Here, the processes of efferocytosis are illustrated and the pathophysiological effects that which occur when this phase is abrogated are highlighted.

scholarly journals Lipid peroxidation and the subsequent cell death transmitting from ferroptotic cells to neighboring cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Hironari Nishizawa ◽  
Mitsuyo Matsumoto ◽  
Guan Chen ◽  
Yusho Ishii ◽  
Keisuke Tada ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Lipid Peroxide ◽  
Nih3t3 Cells ◽  
Regulated Cell Death ◽  
Primary Mouse ◽  
Ischemic Diseases ◽  
A Chain ◽  
Dying Cells

AbstractFerroptosis is a regulated cell death due to the iron-dependent accumulation of lipid peroxide. Ferroptosis is known to constitute the pathology of ischemic diseases, neurodegenerative diseases, and steatohepatitis and also works as a suppressing mechanism against cancer. However, how ferroptotic cells affect surrounding cells remains elusive. We herein report the transfer phenomenon of lipid peroxidation and cell death from ferroptotic cells to nearby cells that are not exposed to ferroptotic inducers (FINs). While primary mouse embryonic fibroblasts (MEFs) and NIH3T3 cells contained senescence-associated β-galactosidase (SA-β-gal)-positive cells, they were decreased upon induction of ferroptosis with FINs. The SA-β-gal decrease was inhibited by ferroptotic inhibitors and knockdown of Atg7, pointing to the involvement of lipid peroxidation and activated autophagosome formation during ferroptosis. A transfer of cell culture medium of cells treated with FINs, type 1 or 2, caused the reduction in SA-β-gal-positive cells in recipient cells that had not been exposed to FINs. Real-time imaging of Kusabira Orange-marked reporter MEFs cocultured with ferroptotic cells showed the generation of lipid peroxide and deaths of the reporter cells. These results indicate that lipid peroxidation and its aftereffects propagate from ferroptotic cells to surrounding cells, even when the surrounding cells are not exposed to FINs. Ferroptotic cells are not merely dying cells but also work as signal transmitters inducing a chain of further ferroptosis.

scholarly journals Autonomous and non-autonomous roles of DNase II during cell death in C. elegans embryos

2015 ◽  
Vol 35 (3) ◽  
Author(s):  
Hsiang Yu ◽  
Huey-Jen Lai ◽  
Tai-Wei Lin ◽  
Szecheng J. Lo
Keyword(s):  
Cell Death ◽  
Caenorhabditis Elegans ◽  
Fluorescence Probes ◽  
Dna Fragments ◽  
Dnase Ii ◽  
C Elegans ◽  
Dying Cells

The method of ToLFP (topoisomerase labelled fluorescence probes) is useful for detecting the DNA fragments generated by DNase II in Caenorhabditis elegans embryos. It reveals ~70% ToLFP signals in dying cells and 30% in engulfing cells during embryogenesis.

Silencing of epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1)viasiRNA-induced cell death in glioblastoma

2016 ◽  
Vol 38 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Florentina Serban ◽  
Oana Daianu ◽  
Ligia Gabriela Tataranu ◽  
Stefan-Alexandru Artene ◽  
Ghazaleh Emami ◽  
...  
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transmembrane Domain ◽  
Epidermal Growth

scholarly journals Insertion of the βGeo Promoter Trap into the Fem1c Gene of ROSA3 Mice

2004 ◽  
Vol 24 (9) ◽  
pp. 3794-3803 ◽  
Author(s):  
Cassandra L. Schlamp ◽  
Andrew T. Thliveris ◽  
Yan Li ◽  
Louis P. Kohl ◽  
Claudia Knop ◽  
...  
Keyword(s):  
Cell Death ◽  
Ganglion Cells ◽  
Neuronal Cell Death ◽  
Insertion Site ◽  
Neuronal Cell ◽  
Pyramidal Cells ◽  
Coding Region ◽  
Protein Levels ◽  
Molecular Events ◽  
Promoter Trap

ABSTRACT ROSA3 mice were developed by retroviral insertion of the βGeo gene trap vector. Adult ROSA3 mice exhibit widespread expression of the trap gene in epithelial cells found in most organs. In the central nervous system the highest expression of βGeo is found in CA1 pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, and ganglion cells of the retina. Characterization of the genomic insertion site for βGeo in ROSA3 mice shows that the trap vector is located in the first intron of Fem1c, a gene homologous to the sex-determining gene fem-1 of Caenorhabditis elegans. Transcription of the Rosa3 allele (R3) yields a spliced message that includes the first exon of Fem1c and the βGeo coding region. Although normal processing of the Fem1c transcript is disrupted in homozygous Rosa3 (Fem1cR3/R3 ) mice, some tissues show low levels of a partially processed transcript containing exons 2 and 3. Since the entire coding region of Fem1c is located in these two exons, Fem1cR3/R3 mice may still be able to express a putative FEM1C protein. To this extent, Fem1cR3/R3 mice show no adverse effects in their sexual development or fertility or in the attenuation of neuronal cell death, another function that has been attributed to both fem-1 and a second mouse homolog, Fem1b. Examination of βGeo expression in ganglion cells after exposure to damaging stimuli indicates that protein levels are rapidly depleted prior to cell death, making the βGeo reporter gene a potentially useful marker to study early molecular events in damaged neurons.

scholarly journals A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Muhammad Babar Khawar ◽  
Muddasir Hassan Abbasi ◽  
Mussarat Rafiq ◽  
Naila Naz ◽  
Rabia Mehmood ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Droplets ◽  
Lysosomal Enzymes ◽  
Lipid Homeostasis ◽  
Cellular Lipid ◽  
Biological Functions ◽  
Lysosomal Function ◽  
Selective Autophagy ◽  
Cellular Components ◽  
Different Levels

Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.

scholarly journals Molecular interactions of autophagy with the immune system and cancer

2017 ◽  
Author(s):  
Yonggeun Hong ◽  
Yunho Jin ◽  
Yunkyung Hong ◽  
Chanyoung Park
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Human Cancer ◽  
Therapeutic Option ◽  
Cancer Cell Line ◽  
Tissue Type ◽  
Alternative Source ◽  
Cancer Cell Death ◽  
Cell Tissue ◽  
Cellular Components

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

scholarly journals Cells differentiating into neuroectoderm undergo apoptosis in the absence of functional retinoblastoma family proteins.

1995 ◽  
Vol 129 (3) ◽  
pp. 779-788 ◽  
Author(s):  
R S Slack ◽  
I S Skerjanc ◽  
B Lach ◽  
J Craig ◽  
K Jardine ◽  
...  
Keyword(s):  
Cell Death ◽  
P19 Cells ◽  
Adenovirus E1a ◽  
Genes Encoding ◽  
Extensive Cell Death ◽  
Extensive Cell ◽  
Early Mouse ◽  
Dying Cells ◽  
Related Proteins ◽  
E1a Protein

The retinoblastoma (RB) protein is present at low levels in early mouse embryos and in pluripotent P19 embryonal carcinoma cells; however, the levels of RB rise dramatically in neuroectoderm formed both in embryos and in differentiating cultures of P19 cells. To investigate the effect of inactivating RB and related proteins p107 and p130, we transfected P19 cells with genes encoding mutated versions of the adenovirus E1A protein that bind RB and related proteins. When these E1A-expressing P19 cells were induced to differentiate into neuroectoderm, there was a striking rise in the expression of c-fos and extensive cell death. The ultrastructural and biochemical characteristics of the dying cells were indicative of apoptosis. The dying cells were those committed to the neural lineages because neurons and astrocytes were lost from differentiating cultures. Cell death was dependent on the ability of the E1A protein to bind RB and related proteins. Our results suggest that proteins of the RB family are essential for the development of the neural lineages and that the absence of functional RB activity triggers apoptosis of differentiating neuroectodermal cells.

scholarly journals STIM1 deficiency is linked to Alzheimer’s disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca2+ entry

2018 ◽  
Vol 96 (10) ◽  
pp. 1061-1079 ◽  
Author(s):  
Carlos Pascual-Caro ◽  
Maria Berrocal ◽  
Aida M. Lopez-Guerrero ◽  
Alberto Alvarez-Barrientos ◽  
Eulalia Pozo-Guisado ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Protein Expression ◽  
Transmembrane Domain ◽  
Neuroblastoma Cell ◽  
Disease Patient ◽  
List Type

Abstract STIM1 is an endoplasmic reticulum protein with a role in Ca2+ mobilization and signaling. As a sensor of intraluminal Ca2+ levels, STIM1 modulates plasma membrane Ca2+ channels to regulate Ca2+ entry. In neuroblastoma SH-SY5Y cells and in familial Alzheimer’s disease patient skin fibroblasts, STIM1 is cleaved at the transmembrane domain by the presenilin-1-associated γ-secretase, leading to dysregulation of Ca2+ homeostasis. In this report, we investigated expression levels of STIM1 in brain tissues (medium frontal gyrus) of pathologically confirmed Alzheimer’s disease patients, and observed that STIM1 protein expression level decreased with the progression of neurodegeneration. To study the role of STIM1 in neurodegeneration, a strategy was designed to knock-out the expression of STIM1 gene in the SH-SY5Y neuroblastoma cell line by CRISPR/Cas9-mediated genome editing, as an in vitro model to examine the phenotype of STIM1-deficient neuronal cells. It was proved that, while STIM1 is not required for the differentiation of SH-SY5Y cells, it is absolutely essential for cell survival in differentiating cells. Differentiated STIM1-KO cells showed a significant decrease of mitochondrial respiratory chain complex I activity, mitochondrial inner membrane depolarization, reduced mitochondrial free Ca2+ concentration, and higher levels of senescence as compared with wild-type cells. In parallel, STIM1-KO cells showed a potentiated Ca2+ entry in response to depolarization, which was sensitive to nifedipine, pointing to L-type voltage-operated Ca2+ channels as mediators of the upregulated Ca2+ entry. The stable knocking-down of CACNA1C transcripts restored mitochondrial function, increased mitochondrial Ca2+ levels, and dropped senescence to basal levels, demonstrating the essential role of the upregulation of voltage-operated Ca2+ entry through Cav1.2 channels in STIM1-deficient SH-SY5Y cell death. Key messages STIM1 protein expression decreases with the progression of neurodegeneration in Alzheimer’s disease. STIM1 is essential for cell viability in differentiated SH-SY5Y cells. STIM1 deficiency triggers voltage-regulated Ca2+ entry-dependent cell death. Mitochondrial dysfunction and senescence are features of STIM1-deficient differentiated cells.

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