The molecular machinery of regulated cell death

Cell Research, Год журнала: 2019, Номер 29(5), С. 347 - 364

Опубликована: Апрель 4, 2019

Cells may die from accidental cell death (ACD) or regulated (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms have been identified are increasingly being implicated in various human pathologies. Here, we critically review the current state art regarding types RCD, including necroptosis, pyroptosis, ferroptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis oxeiptosis. The in-depth comprehension each these lethal subroutines their intercellular consequences uncover therapeutic targets for avoidance pathogenic loss.

Язык: Английский

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Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cell Death and Differentiation, Год журнала: 2014, Номер 22(1), С. 58 - 73

Опубликована: Сен. 19, 2014

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such unavoidable variant cellular demise is generally referred 'accidental cell death' (ACD). In most settings, however, death initiated by genetically encoded apparatus, correlating with the fact that its course can be altered pharmacologic genetic interventions. 'Regulated (RCD) occur part physiologic programs activated once adaptive responses perturbations extracellular intracellular microenvironment fail. The biochemical phenomena accompany RCD may harnessed classify it into few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting processes are commonly thought cause RCD, such activation executioner caspases apoptosis, does exert true cytoprotective effects mammalian system, but simply alters kinetics shifts and correlates. Conversely, bona fide cytoprotection achieved transduction lethal signals early phases process, when still operational. Thus, mechanisms truly execute less understood, inhibitable perhaps more homogeneous than previously thought. Here, Nomenclature Committee on Cell Death formulates set recommendations help scientists researchers discriminate between essential accessory aspects death.

Язык: Английский

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HMGB1 in health and disease

Molecular Aspects of Medicine, Год журнала: 2014, Номер 40, С. 1 - 116

Опубликована: Июль 8, 2014

Язык: Английский

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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Journal for ImmunoTherapy of Cancer, Год журнала: 2020, Номер 8(1), С. e000337 - e000337

Опубликована: Март 1, 2020

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular microenvironmental features determine the propensity of RCD drive immunity. Here, we provide updated operational definition immunogenic (ICD), discuss key factors that dictate ability dying cells response, summarize experimental assays are currently available for assessment ICD in vitro vivo, formulate guidelines their interpretation.

Язык: Английский

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Consensus guidelines for the detection of immunogenic cell death

OncoImmunology, Год журнала: 2014, Номер 3(9), С. e955691 - e955691

Опубликована: Сен. 2, 2014

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm system, which we named "immunogenic cell death" (ICD). ICD is preceded accompanied emission series immunostimulatory damage-associated molecular patterns (DAMPs) in precise spatiotemporal configuration. Several anticancer agents successfully employed clinic decades, including various chemotherapeutics and radiotherapy, ICD. Moreover, defects components underlie capacity system perceive death immunogenic negatively influence disease outcome among cancer patients treated with inducers. Thus, has profound clinical therapeutic implications. Unfortunately, gold-standard approach detect relies on vaccination experiments involving immunocompetent murine models syngeneic cells, an incompatible large screening campaigns. Here, outline strategies conceived surrogate markers vitro screen chemical libraries putative inducers, based high-content, high-throughput platform recently developed. Such allows detection DAMPs, like surface-exposed calreticulin, extracellular ATP high mobility group box 1 (HMGB1), and/or processes their emission, such endoplasmic reticulum stress, autophagy necrotic plasma membrane permeabilization. We surmise this technology will facilitate development next-generation regimens, kill malignant simultaneously convert them into cancer-specific vaccine.

Язык: Английский

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Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns

Journal of Biological Chemistry, Год журнала: 2014, Номер 289(51), С. 35237 - 35245

Опубликована: Ноя. 13, 2014

Язык: Английский

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The tumor suppressor protein p53 and the ferroptosis network

Free Radical Biology and Medicine, Год журнала: 2018, Номер 133, С. 162 - 168

Опубликована: Май 23, 2018

Язык: Английский

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Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein

Autophagy, Год журнала: 2020, Номер 16(11), С. 2069 - 2083

Опубликована: Янв. 10, 2020

is the most frequently mutated oncogene in human neoplasia. Despite a large investment to understand effects of KRAS mutation cancer cells, direct oncogenetic activation on immune cells remain elusive. Here, we report that extracellular

Язык: Английский

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Release and activity of histone in diseases

Cell Death and Disease, Год журнала: 2014, Номер 5(8), С. e1370 - e1370

Опубликована: Авг. 14, 2014

Histones and their post-translational modifications have key roles in chromatin remodeling gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous to animals leads systemic inflammatory toxic responses through activating Toll-like receptors inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies, activated protein C, recombinant thrombomodulin, heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, thrombosis. In addition, elevated serum histone nucleosome levels been implicated multiple pathophysiological processes progression diseases including autoimmune diseases, cancer. Therefore, could serve biomarkers novel therapeutic targets human diseases.

Язык: Английский

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Cell death due to electroporation – A review

Bioelectrochemistry, Год журнала: 2021, Номер 141, С. 107871 - 107871

Опубликована: Июнь 5, 2021

Exposure of cells to high voltage electric pulses increases transiently membrane permeability through electroporation. Electroporation can be reversible and is used in gene transfer enhanced drug delivery but also lead cell death. resulting death (termed as irreversible electroporation) has been successfully a new non-thermal ablation method soft tissue such tumours or arrhythmogenic heart tissue. Even though the mechanisms influence outcome electroporation-based treatments due use different pulse parameters conditions, these are not elucidated yet. We review after electroporation reported literature, injuries that may repair involved. The knowledge exposure pulses, targets field need identified optimize existing develop techniques medicine, biotechnology, food technology.

Язык: Английский

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