scholarly journals Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of Ranbp2 in Cone Photoreceptors

PLoS Genetics ◽  
2013 ◽  
Vol 9 (6) ◽  
pp. e1003555 ◽  
Author(s):  
Kyoung-in Cho ◽  
MdEmdadul Haque ◽  
Jessica Wang ◽  
Minzhong Yu ◽  
Ying Hao ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Cell Types ◽  
Cone Photoreceptors ◽  
Cell Death Pathways

scholarly journals PANoptosis: A New Insight Into Oral Infectious Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiyi Jiang ◽  
Zilong Deng ◽  
Xingzhu Dai ◽  
Wanghong Zhao
Keyword(s):  
Cell Death ◽  
Infectious Diseases ◽  
Classical Model ◽  
Cell Types ◽  
Oral Microbiome ◽  
Host Cells ◽  
Tissue Destruction ◽  
Death Studies ◽  
Cell Death Pathways ◽  
Single Term

The oral microbiome, one of the most complex and intensive microbial ecosystems in the human body, comprises bacteria, archaea, fungi, protozoa, and viruses. Dysbiosis of the oral microbiome is the initiating factor that leads to oral infectious diseases. Infection is a sophisticated biological process involving interplay between the pathogen and the host, which often leads to activation of programmed cell death. Studies suggest that pyroptosis, apoptosis, and necroptosis are involved in multiple oral infectious diseases. Further understanding of crosstalk between cell death pathways has led to pyroptosis, apoptosis, and necroptosis being integrated into a single term: PANoptosis. PANoptosis is a multifaceted agent of the immune response that has important pathophysiological relevance to infectious diseases, autoimmunity, and cancer. As such, it plays an important role in innate immune cells that detect and eliminate intracellular pathogens. In addition to the classical model of influenza virus-infected and Yersinia-infected macrophages, other studies have expanded the scope of PANoptosis to include other microorganisms, as well as potential roles in cell types other than macrophages. In this review, we will summarize the pathophysiological mechanisms underlying inflammation and tissue destruction caused by oral pathogens. We present an overview of different pathogens that may induce activation of PANoptosis, along with the functional consequences of PANoptosis in the context of oral infectious diseases. To advance our understanding of immunology, we also explore the strategies used by microbes that enable immune evasion and replication within host cells. Improved understanding of the interplay between the host and pathogen through PANoptosis will direct development of therapeutic strategies that target oral infectious diseases.

Presenilin-interacting proteins

2002 ◽  
Vol 4 (19) ◽  
pp. 1-18 ◽  
Author(s):  
Qi Chen ◽  
David Schubert
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Cell Types ◽  
Cellular Adhesion ◽  
Interacting Proteins ◽  
Missense Mutations ◽  
Cell Death Pathways ◽  
Physiological Relevance ◽  
Genes Encoding

Familial Alzheimer's disease (FAD) accounts for 5–10% of deaths from Alzheimer's disease (AD), and approximately 50% of these cases have been definitely linked to missense mutations in three genes, encoding the amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2). Of these, the vast majority of FAD-linked mutations are within PS1. There has been an extensive effort to identify proteins that functionally interact with PS1 and PS2 because of their clear roles in FAD. The goal of this review is to describe these proteins and to discuss in more detail the probable biological functions of a subset of the better-studied interacting proteins. In particular, the review examines APP, Notch, nicastrin, modifier of cellular adhesion (MOCA), β-catenin, and the group of proteins involved in cell death, calcium metabolism and cell adhesion. We argue that, although a few of the interacting proteins are unambiguously involved in well-studied cellular pathways, their exact roles within these pathways have not been clearly defined, and indeed might vary between cell types. We also question the physiological relevance of some of the work linking PS to cell death pathways. Finally, we point out the value of using flies and worms to sort out the often contradictory work in the PS field, and we mention how knowledge of PS-interacting pathways will contribute to the development of new therapeutic strategies in AD.

Molecular Determinants of Bendamustine (BDM) Toxicity towards Hodgkin (H) and Reed-Sternberg (RS) Cell Lines From Hodgkin Lymphoma (HL).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2763-2763
Author(s):  
Rosaria De Filippi ◽  
Stefania Crisci ◽  
Ferdinando Frigeri ◽  
Donatella Aldinucci ◽  
Domenico Galati ◽  
...  
Keyword(s):  
Cell Death ◽  
Dna Repair ◽  
Cell Lines ◽  
Cell Types ◽  
Cyclin B1 ◽  
Mitotic Catastrophe ◽  
Dna Repair Genes ◽  
Cell Death Pathways ◽  
Dose Dependent ◽  
Repair Genes

Abstract Abstract 2763 Patients with HL recurring after stem cell transplantation (SCT) are mostly incurable. Therefore development of new agents and strategies is an impellent medical need in this setting. BDM is a hybrid purine analogue/bi-functional alkylator active in B-cell tumors. Despite preliminary evidences of efficacy in refractory HL, the molecular mechanisms underlying the potential activity of BDM towards malignant H-RS cells were never explored. We investigated patterns of BDM cytotoxicity (12.5 to 100 mmol/L) in a panel of HL-derived cell lines (L1236, L428, KMH2, HDLM2, L540) and its time-dependent (8, 24, 48, 72 hrs) effects on genes involved in DNA-damage stress and repair response, apoptosis and cell cycle checkpoints by Q-RT-PCR. BDM induced a significant time- and dose-dependent inhibition of growth and survival in all cell types. L1236 cells displayed the highest sensitivity to the agent with an IC50, at 48 hrs, of 10.7 mmol/L, as opposed to KMH2, L428, L540 and HDLM2 cells with IC50 of 11.1, 12.4, 14.8 and 16.2 mmol/L, respectively. BDM elicited a dose-dependent increase of apoptosis (30% to 50% at 72 hrs) in all cell lines, as shown by Annexin-V/propidium iodide staining. The exquisite sensitivity to BDM of L1236 cells was confirmed by clonogenic assays, since these cells, after a 24 hr exposure, showed the lowest IC50 for secondary colony formation (0.7± 0.06 mmol/L) as compared to all other cell lines (IC50 range: 3.1 ± 0.28 to 15.0 ± 1.27 mmol/L). Most notably, however, BDM, within the same concentration range, activated different cell death subroutines among the various cell lines. Q-RT-PCR disclosed that BDM-induced cell death in L1236 was mainly dependent on triggering of apoptosis, as shown by the early (8–24 hrs) up regulation of the proapoptotic genes NOXA and p21, but not p27, without appreciable changes in expression levels of genes related to activation of the mitotic catastrophe process, i.e. PLK1, Aurora A kinase (AAK), and cyclin B1. In contrast, induction of mitotic catastrophe was a main determinant of BDM action on KMH2, L428 and L540 cells, as shown by early (8 hrs) and sustained (48 hrs) down-regulation of PLK1, AAK and cyclin B1 genes, without early changes in NOXA and p21 expression levels. This was confirmed by highly aberrant mitosis and further multinucleation. Interestingly, BDM induced the sequential activation of both these cell death pathways in HDLM2 cells only. In this cells, the early (8–24 hrs) down regulation of PLK1, AAK and cyclin B1 genes, was later (48–72 hrs) followed by a significant induction of NOXA, p21 and p27 genes. The highest sensitivity of L1236 cells to BDM correlated with the delayed (72 hrs) induction of the DNA-repair genes EXO-1 and ATR, but not ATM, as opposed to the earlier (24 hrs) and sustained up regulation of these DNA-repair genes, and of ATM, in all other cell types. Accordingly, only after 72 hrs from exposure to BDM, the proliferation-related genes C-MYC, E2F2 and cyclins (D1, D2) were up regulated in surviving L1236 cells, along with a >70% reduction in G0/G1 cells, a significant (48%) increase of cells in the G2 phase of the cell cycle and a 20% increment of those in S phase. Conversely, in the other cell lines, S phase accumulation (35% to 60.5% increase) and up regulation of proliferation-related genes in surviving cells occurred, as early as 24 hrs after exposure to BDM. Overall, these results indicate that BDM affects different cell death pathways among HL-derived cell lines. Specifically, in L1236 cells the agent induces the early up regulation of proapototic genes and G2 arrest, accompanied by a delayed activation of DNA repair genes. This changes may lead to cell death through apoptosis rather than mitotic catastrophe which, conversely, appeared the predominant cell death pathway activated by BDM in the other cell lines. Notably, while determinants of BDM toxicity in ‘bona fide’ HL cell lines consistently overlap with those described for tumor B-cells of non-Hodgkin lymphomas (mitotic catastrophe), L1236 cells display a different response pattern to the agent, more reminiscent of BDM action on myeloma tumor cells. Since only L1236 cells are clonotypically related to primary H-RS cells from which were derived, our results suggest that optimal BDM dosing and scheduling in HL may be different from those adopted for other B-cell tumors. In this sense, a lower BDM dosing through a weekly schedule is currently being tested at our institution in refractory HL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

2021 ◽  
Author(s):  
Akanksha Roy ◽  
Arianna Tolone ◽  
Riet Hilhorst ◽  
John Groten ◽  
Tushar Tomar ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Guanosine Monophosphate ◽  
Disease Genes ◽  
Ionotropic Receptor ◽  
Downstream Targets ◽  
Activity Profiling

AbstractInherited retinal diseases (IRDs) are a group of neurodegenerative disorders that lead to photoreceptor cell death and eventually blindness. IRDs are characterised by a high genetic heterogeneity, making it imperative to design mutation-independent therapies. Mutations in a number of IRD disease genes have been associated with a rise of cyclic 3’,5’-guanosine monophosphate (cGMP) levels in photoreceptors. Accordingly, the cGMP-dependent protein kinase (PKG) has emerged as a new potential target for the mutation-independent treatment of IRDs. However, the substrates of PKG and the downstream degenerative pathways triggered by its activity have yet to be determined. Here, we performed kinome activity profiling of different murine organotypic retinal explant cultures (diseased rd1 and wild-type controls) using multiplex peptide microarrays to identify proteins whose phosphorylation was significantly altered by PKG activity. In addition, we tested the downstream effect of a known PKG inhibitor CN03 in these organotypic retina cultures. Among the PKG substrates were potassium channels belonging to the Kv1 family (KCNA3, KCNA6), Cyclic AMP-responsive element-binding protein 1 (CREB1), DNA topoisomerase 2-α (TOP2A), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263), and the glutamate ionotropic receptor kainate 2 (GRIK2). The retinal expression of these PKG targets was further confirmed by immunofluorescence and could be assigned to various neuronal cell types, including photoreceptors, horizontal cells, and ganglion cells. Taken together, this study confirmed the key role of PKG in photoreceptor cell death and identified new downstream targets of cGMP/PKG signalling that will improve the understanding of the degenerative mechanisms underlying IRDs.

scholarly journals Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2

2015 ◽  
Vol 83 (9) ◽  
pp. 3410-3417 ◽  
Author(s):  
Kathleen Nudel ◽  
Paola Massari ◽  
Caroline A. Genco
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Neisseria Gonorrhoeae ◽  
Cell Types ◽  
Transmitted Infection ◽  
Content Type ◽  
Sexually Transmitted ◽  
Cell Death Pathways ◽  
Host Cell Death ◽  
Cervical Epithelial Cells

Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated thatNeisseria gonorrhoeae, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death byN. gonorrhoeaehas also been reported in other cell types. The mechanisms by whichN. gonorrhoeaemodulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed thatN. gonorrhoeaeinduces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early afterN. gonorrhoeaestimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 inN. gonorrhoeae-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate thatN. gonorrhoeaestimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling.

scholarly journals Hypoxia-Driven Immune Escape in the Tumor Microenvironment

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 992 ◽  
Author(s):  
Alyssa Vito ◽  
Nader El-Sayes ◽  
Karen Mossman
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cell Types ◽  
Cell Death Pathways ◽  
Hypoxic Conditions ◽  
Complex Ecosystem ◽  
Different Cell Types ◽  
Immune Detection ◽  
Immunosuppressive Cytokines

The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways.

scholarly journals Photoreceptor Cell Death, Proliferation and Formation of Hybrid Rod/S-Cone Photoreceptors in the Degenerating STK38L Mutant Retina

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24074 ◽  
Author(s):  
Ágnes I. Berta ◽  
Kathleen Boesze-Battaglia ◽  
Sem Genini ◽  
Orly Goldstein ◽  
Paul J. O'Brien ◽  
...  
Keyword(s):  
Cell Death ◽  
Photoreceptor Cell ◽  
Cone Photoreceptors

Development and Challenges of Nanotherapeutic Formulations for Targeting Mitochondrial Cell Death Pathways in Lung and Brain Degenerative Diseases

2020 ◽  
Vol 48 (3) ◽  
pp. 137-152
Author(s):  
Marko Manevski ◽  
Dinesh Devadoss ◽  
Ruben Castro ◽  
Lauren Delatorre ◽  
Adriana Yndart ◽  
...  
Keyword(s):  
Cell Death ◽  
Degenerative Diseases ◽  
Cell Death Pathways

Proteomic Analysis of Exosomes Released from Heatstressed Hepatocytes Reveals Promotion of Programmed Cell Death Pathways

2018 ◽  
Author(s):  
Yue Li ◽  
Xintao Zhu ◽  
Guozhen Wang ◽  
Huasheng Tong ◽  
Xuguang Ling ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Proteomic Analysis ◽  
Cell Death Pathways
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