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https://www.readbyqxmd.com/read/29352166/epstein-barr-virus-encoded-latent-membrane-protein-1-suppresses-necroptosis-through-targeting-ripk1-3-ubiquitination
#1
Xiaolan Liu, Yueshuo Li, Songling Peng, Xinfang Yu, Wei Li, Feng Shi, Xiangjian Luo, Min Tang, Zheqiong Tan, A M Bode, Ya Cao
Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29337619/the-role-of-necroptosis-apoptosis-and-inflammation-in-fowl-cholera-associated-liver-injury-in-a-chicken-model
#2
Qiyu Tang, Weitian Li, Na Dai, Yiming Gao, Yu Han, Guofu Cheng, Changqin Gu
Fowl cholera resulting from infection with Pasteurella multocida causes huge economic losses in the poultry industry. Necrotic hepatitis is reported to be a significant lesion associated with fowl cholera in chickens. Clarifying the underlying molecular mechanism of hepatic injury caused by P. multocida infection is needed to develop new strategies to control fowl cholera. Pasteurella multocida Q (the standard reference strain) and P. multocida 1G1 (a clinical strain) were used to infect healthy laying hens...
December 2017: Avian Diseases
https://www.readbyqxmd.com/read/29331741/extracellular-acidification-induces-ros-and-mptp-mediated-death-in-hek293-cells
#3
José Teixeira, Farhan Basit, Herman G Swarts, Marleen Forkink, Paulo J Oliveira, Peter H G M Willems, Werner J H Koopman
The extracellular pH (pHe) is a key determinant of the cellular (micro)environment and needs to be maintained within strict boundaries to allow normal cell function. Here we used HEK293 cells to study the effects of pHe acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A) and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell viability by 70% and was paralleled by a decrease in cytosolic pH (pHc), hyperpolarization of the mitochondrial membrane potential (Δψ), increased levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29317761/mk2-puts-an-additional-brake-on-ripk1-cytotoxic-potential
#4
Yves Dondelinger, Tom Delanghe, Mathieu M J Bertrand
No abstract text is available yet for this article.
January 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29317521/ca2-dependent-demethylation-of-phosphatase-pp2ac-promotes-glucose-deprivation-induced-cell-death-independently-of-inhibiting-glycolysis
#5
Ha Yin Lee, Yoko Itahana, Stefan Schuechner, Masahiro Fukuda, H Shawn Je, Egon Ogris, David M Virshup, Koji Itahana
Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1...
January 9, 2018: Science Signaling
https://www.readbyqxmd.com/read/29275999/mk2-tnf-signaling-comes-full-circle
#6
REVIEW
Manoj B Menon, Matthias Gaestel
MK2 (p38MAPK-activated protein kinase 2) is essential for tumor necrosis factor (TNF) biosynthesis, mainly operating by post-transcriptional regulation. Deletion of the gene encoding MK2 strongly reduced serum TNF and protected against endotoxic shock, demonstrating the positive role of p38MAPK/MK2 in TNF signaling at the level of ligand expression. Recent evidence indicates that MK2 directly phosphorylates the TNF receptor interactor RIPK1 and suppresses its activity, thereby limiting TNF-mediated apoptosis and necroptosis - pointing to a more complex, double-edged role of MK2 in TNF signaling...
December 21, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#7
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29247776/necrostatin-1-improves-long-term-functional-recovery-through-protecting-oligodendrocyte-precursor-cells-after-transient-focal-cerebral-ischemia-in-mice
#8
Yingzhu Chen, Lingling Zhang, Hailong Yu, Kangping Song, Jinling Shi, Linlin Chen, Jian Cheng
Ischemic stroke often results in severe injury to white matter structures including the axons, oligodendroglia, and other glial cells. Immature stages of oligodendroglia, such as oligodendrocyte precursor cells (OPCs) and premature oligodendroglia, are more vulnerable to ischemia than mature oligodendroglia. Extensive studies have been performed on the necroptosis of neurons following cerebral ischemia. The present study aimed to investigate the effect of necrostatin-1 (Nec-1), a necroptosis inhibitor, on the survival of OPCs and long-term functional recovery following transient cerebral ischemia...
December 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/29238045/ripk3-promotes-adenovirus-type-5-activity
#9
Melanie Weigert, Alex Binks, Suzanne Dowson, Elaine Y L Leung, Dmitris Athineos, Xinzi Yu, Margaret Mullin, Josephine B Walton, Clare Orange, Darren Ennis, Karen Blyth, Stephen W G Tait, Iain A McNeish
Oncolytic adenoviral mutants infect human malignant cells and replicate selectively within them. This induces direct cytotoxicity that can also trigger profound innate and adaptive immune responses. However, the mechanism by which adenoviruses produce cell death remains uncertain. We previously suggested that type 5 adenoviruses, including the E1A CR2 deletion mutant dl922-947, might induce a novel form of programmed death resembling necroptosis. Here we have investigated the roles of core necrosis proteins RIPK1, RIPK3 and MLKL in the cytotoxicity of dl922-947 and other adenovirus serotypes...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29229989/necroptotic-signaling-is-primed-in-mycobacterium-tuberculosis-infected-macrophages-but-its-pathophysiological-consequence-in-disease-is-restricted
#10
Michael D Stutz, Samar Ojaimi, Cody Allison, Simon Preston, Philip Arandjelovic, Joanne M Hildebrand, Jarrod J Sandow, Andrew I Webb, John Silke, Warren S Alexander, Marc Pellegrini
Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29226626/randomized-clinical-study-of-safety-pharmacokinetics-and-pharmacodynamics-of-ripk1-inhibitor-gsk2982772-in-healthy-volunteers
#11
Kathleen Weisel, Nicola E Scott, Debra J Tompson, Bartholomew J Votta, Sujith Madhavan, Kat Povey, Allen Wolstenholme, Monica Simeoni, Todd Rudo, Lauren Richards-Peterson, Tarjinder Sahota, J Gene Wang, John Lich, Joshua Finger, Adeline Verticelli, Michael Reilly, Peter J Gough, Philip A Harris, John Bertin, Mei-Lun Wang
GSK2982772 is a highly selective inhibitor of receptor-interacting protein kinase 1 (RIPK1) being developed to treat chronic inflammatory diseases. This first-in-human study evaluated safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of GSK2982772 administered orally to healthy male volunteers. This was a Phase I, randomized, placebo-controlled, double-blind study. In Part A, subjects received single ascending doses of GSK2982772 (0.1-120 mg) or placebo in a crossover design during each of 4 treatment periods...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29226625/identification-of-an-antibody-based-immunoassay-for-measuring-direct-target-binding-of-ripk1-inhibitors-in-cells-and-tissues
#12
Joshua N Finger, Jean-Marie Brusq, Nino Campobasso, Michael N Cook, Jennifer Deutsch, Heather Haag, Philip A Harris, Earl L Jenkins, Devika Joglekar, John D Lich, Sean Maguire, Rakesh Nagilla, Elizabeth J Rivera, Helen Sun, Bartholomew J Votta, John Bertin, Peter J Gough
Therapies that suppress RIPK1 kinase activity are emerging as promising therapeutic agents for the treatment of multiple inflammatory disorders. The ability to directly measure drug binding of a RIPK1 inhibitor to its target is critical for providing insight into pharmacokinetics, pharmacodynamics, safety and clinical efficacy, especially for a first-in-class small-molecule inhibitor where the mechanism has yet to be explored. Here, we report a novel method for measuring drug binding to RIPK1 protein in cells and tissues...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29217118/checkpoints-in-tnf-induced-cell-death-implications-in-inflammation-and-cancer
#13
REVIEW
Alessandro Annibaldi, Pascal Meier
Tumor necrosis factor (TNF) is a proinflammatory cytokine that coordinates tissue homeostasis by regulating cytokine production, cell survival, and cell death. However, how life and death decisions are made in response to TNF is poorly understood. Many inflammatory pathologies are now recognized to be driven by aberrant TNF-induced cell death, which, in most circumstances, depends on the kinase Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Recent advances have identified ubiquitin (Ub)-mediated phosphorylation of RIPK1 as belonging to crucial checkpoints for cell fate in inflammation and infection...
December 4, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29212904/dendritic-cell-ripk1-maintains-immune-homeostasis-by-preventing-inflammation-and-autoimmunity
#14
Joanne A O'Donnell, Jesse Lehman, Justine E Roderick, Dalia Martinez-Marin, Matija Zelic, Ciara Doran, Nicole Hermance, Stephen Lyle, Manolis Pasparakis, Katherine A Fitzgerald, Ann Marshak-Rothstein, Michelle A Kelliher
Necroptosis is a form of cell death associated with inflammation; however, the biological consequences of chronic necroptosis are unknown. Necroptosis is mediated by RIPK1, RIPK3, and MLKL kinases but in hematopoietic cells RIPK1 has anti-inflammatory roles and functions to prevent necroptosis. Here we interrogate the consequences of chronic necroptosis on immune homeostasis by deleting Ripk1 in mouse dendritic cells. We demonstrate that deregulated necroptosis results in systemic inflammation, tissue fibrosis, and autoimmunity...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29203883/abin-1-regulates-ripk1-activation-by-linking-met1-ubiquitylation-with-lys63-deubiquitylation-in-tnf-rsc
#15
Slawomir A Dziedzic, Zhenyi Su, Vica Jean Barrett, Ayaz Najafov, Adnan K Mookhtiar, Palak Amin, Heling Pan, Li Sun, Hong Zhu, Averil Ma, Derek W Abbott, Junying Yuan
Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1...
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29200200/wogonin-protects-against-cisplatin-induced-acute-kidney-injury-by-targeting-ripk1-mediated-necroptosis
#16
Xiao-Ming Meng, Hai-Di Li, Wei-Feng Wu, Patrick Ming-Kuen Tang, Gui-Ling Ren, Li Gao, Xiao-Feng Li, Yang Yang, Tao Xu, Tao-Tao Ma, Zeng Li, Cheng Huang, Lei Zhang, Xiong-Wen Lv, Jun Li
Acute kidney injury (AKI), characterized by aggressive inflammatory responses and destruction of renal resident cells, can cause abrupt kidney dysfunction. To date, effective therapy for AKI is lacking. In this study, we evaluated the renoprotective effect of wogonin, an herbal active compound, using a cisplatin-induced AKI mouse model. In vivo results show that wogonin substantially suppressed the increased levels of serum creatinine and blood urea nitrogen (BUN) almost to the normal level. Wogonin also attenuated tubular damage, shown by PAS staining, electron microscopy and molecular analysis of KIM-1...
December 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29171784/necroptosis-promotes-autophagy-dependent-upregulation-of-damp-and-results-in-immunosurveillance
#17
Sheng-Yen Lin, Sung-Yuan Hsieh, Yi-Ting Fan, Wen-Chi Wei, Pei-Wen Hsiao, Dai-Hua Tsai, Tzong-Shoon Wu, Ning-Sun Yang
Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity...
November 24, 2017: Autophagy
https://www.readbyqxmd.com/read/29142064/the-resurrection-of-the-piddosome-emerging-roles-in-the-dna-damage-response-and-centrosome-surveillance
#18
REVIEW
Valentina Sladky, Fabian Schuler, Luca L Fava, Andreas Villunger
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29137405/necroptosis-regulated-proteins-expression-is-an-early-prognostic-biomarker-in-patient-with-sepsis-a-prospective-observational-study
#19
Bing Wang, Jian Li, Hong-Mei Gao, Ying-Hong Xing, Zhu Lin, Hong-Jie Li, Yong-Qiang Wang
Background and aim: Increasing researchers indicate that necroptosis is playing an important role in the regulation of systemic inflammatory response syndrome. The current study was to investigate the prognostic biomarker of the regulated proteins of necroptosis in sepsis patients. Results: One hundred and twenty-four patients were divided into three groups: 43 patients (34.68%) with sepsis, 39 patients (31.45%) with severe sepsis, and 42 patients (33.87%) with septic shock...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29123466/neuroprotective-effect-of-%C3%AE-caryophyllene-on-cerebral-ischemia-reperfusion-injury-via-regulation-of-necroptotic-neuronal-death-and-inflammation-in-vivo-and-in-vitro
#20
Mei Yang, Yongjiu Lv, Xiaocui Tian, Jie Lou, Ruidi An, Qian Zhang, Minghang Li, Lu Xu, Zhi Dong
Necrotic cell death is a hallmark feature of ischemic stroke and it may facilitate inflammation by releasing intracellular components after cell-membrane rupture. Previous studies reported that β-caryophyllene (BCP) mitigates cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanism remains unclear. We explored whether BCP exerts a neuroprotective effect in cerebral I/R injury through inhibiting necroptotic cell death and inflammation. Primary neurons with and without BCP (0.2, 1, 5, 25 μM) treatment were exposed to oxygen-glucose deprivation and re-oxygenation (OGD/R)...
2017: Frontiers in Neuroscience
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