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https://www.readbyqxmd.com/read/29334122/inhibition-of-hsp90%C3%AE-protects-cultured-neurons-from-oxygen-glucose-deprivation-induced-necroptosis-by-decreasing-rip3-expression
#1
Zhen Wang, Li-Min Guo, Yong Wang, Hong-Kang Zhou, Shu-Chao Wang, Dan Chen, Ju-Fang Huang, Kun Xiong
Heat shock protein 90α (HSP90α) maintains cell stabilization and regulates cell death, respectively. Recent studies have shown that HSP90α is involved in receptor interacting protein 3 (RIP3)-mediated necroptosis in HT29 cells. It is known that oxygen and glucose deprivation (OGD) can induce necroptosis, which is regulated by RIP3 in neurons. However, it is still unclear whether HSP90α participates in the process of OGD-induced necroptosis in cultured neurons via the regulation of RIP3. Our study found that necroptosis occurs in primary cultured cortical neurons and PC-12 cells following exposure to OGD insult...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29299822/necrostatin-1-protects-against-paraquat-induced-cardiac-contractile-dysfunction-via-rip1-rip3-mlkl-dependent-necroptosis-pathway
#2
Liping Zhang, Qiming Feng, Teng Wang
Paraquat is a highly toxic prooxidant that triggers oxidative stress and multi-organ failure including that of the heart. To date, effective treatment of paraquat toxicity is still not established. Necroptosis, a newly discovered form of programmed cell death, was recently shown to be strongly associated with cardiovascular disease. Receptor interaction proteins 1 (RIP1), receptor interaction proteins 3 (RIP3), and mixed lineage kinase domain like (MLKL) are key proteins in the necroptosis pathway. Necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis which acts by blocking the interaction between RIP1 and RIP3...
January 3, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#3
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
#4
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
#5
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
#6
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/29212904/dendritic-cell-ripk1-maintains-immune-homeostasis-by-preventing-inflammation-and-autoimmunity
#7
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...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29170110/association-of-anti-her2-antibody-with-graphene-oxide-for-curative-treatment-of-osteosarcoma
#8
Lan Li, Chengke Luo, Zhenwei Song, Eduardo Reyes-Vargas, Fred Clayton, Jufang Huang, Peter Jensen, Xinjian Chen
The finding of HER2 overexpression in osteosarcoma (OS) makes HER2 a potential therapeutic target. However, studies indicate OS cells are nonresponsive to anti-HER2 antibody trastuzumab (TRA) therapy. We established stable, non-covalent association of TRA with nanomaterial graphene oxide (GO) to generated multivalent TRA/GO complexes that demonstrated markedly enhanced HER2-binding activity and capacity to rapidly kill OS cells. TRA/GO simultaneously induced oxidative stress and HER2 signaling in the target cells, leading to rapid depletion of the cellular inhibitors of apoptosis protein (cIAP) and caspase 8, formation of RIP1/RIPK3/MLKL necroptosome and necroptosis of the OS cells...
November 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29167229/embryonic-lethality-and-host-immunity-of-rela-deficient-mice-are-mediated-by-both-apoptosis-and-necroptosis
#9
Chengxian Xu, Xiaoxia Wu, Xixi Zhang, Qun Xie, Cunxian Fan, Haibing Zhang
In mammalian cells, signaling pathways triggered by TNF can be switched from NF-κB activation to apoptosis and/or necroptosis. The in vivo mechanisms underlying the mutual regulation of these three signaling pathways are poorly understood. In this article, we report that the embryonic lethality of RelA-deficient mice is partially prevented by the deletion of Rip3 or Mlkl, but it is fully rescued by the combined ablation of Fadd and Rip3 or Mlkl or by blocking RIP1 kinase activity (RIP1K45A). RelA-/-Fadd-/-Rip3-/- triple-knockout (TKO) and RelA-/-Rip1K45A/K45A mice displayed bacterial pneumonia leading to death ∼2 wk after birth...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29156831/protective-effect-of-nsa-on-intestinal-epithelial-cells-in-a-necroptosis-model
#10
Wei Dong, Min Zhang, Yaxi Zhu, Yuanhan Chen, Xingchen Zhao, Ruizhao Li, Li Zhang, Zhiming Ye, Xingling Liang
Objective: This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF-α and Z-VAD-fmk, and the cells were treated with or without NSA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138474/phagocytosis-of-environmental-or-metabolic-crystalline-particles-induces-cytotoxicity-by-triggering-necroptosis-across-a-broad-range-of-particle-size-and-shape
#11
Mohsen Honarpisheh, Orestes Foresto-Neto, Jyaysi Desai, Stefanie Steiger, Lidia Anguiano Gómez, Bastian Popper, Peter Boor, Hans-Joachim Anders, Shrikant R Mulay
In crystallopathies, crystals or crystalline particles of environmental and metabolic origin deposit within tissues, induce inflammation, injury and cell death and eventually lead to organ-failure. The NLRP3-inflammasome is involved in mediating crystalline particles-induced inflammation, but pathways leading to cell death are still unknown. Here, we have used broad range of intrinsic and extrinsic crystal- or crystalline particle-sizes and shapes, e.g. calcium phosphate, silica, titanium dioxide, cholesterol, calcium oxalate, and monosodium urate...
November 14, 2017: Scientific Reports
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
#12
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
https://www.readbyqxmd.com/read/29104146/mlkl-pitp%C3%AE-signaling-mediated-necroptosis-contributes-to-cisplatin-triggered-cell-death-in-lung-cancer-a549-cells
#13
Lin Jing, Fei Song, Zhenyu Liu, Jianghua Li, Bo Wu, Zhiguang Fu, Jianli Jiang, Zhinan Chen
Necroptosis has been reported to be involved in cisplatin-induced cell death, but the mechanisms underlying the occurrence of necroptosis are not fully elucidated. In this study, we show that apart from apoptosis, cisplatin induces necroptosis in A549 cells. The alleviation of cell death by two necroptosis inhibitors-necrostatin-1 (Nec-1) and necrosulfonamide (NSA), and the phosphorylation of mixed lineage kinase domain-like protein (MLKL) at serine 358, suggest the involvement of receptor-interacting protein kinase 1 (RIPK1)-RIPK3-MLKL signaling in cisplatin-treated A549 cells...
November 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29103102/combination-of-emricasan-with-ponatinib-synergistically-reduces-ischemia-reperfusion-injury-in-rat-brain-through-simultaneous-prevention-of-apoptosis-and-necroptosis
#14
Jing Tian, Shu Guo, Heng Chen, Jing-Jie Peng, Miao-Miao Jia, Nian-Sheng Li, Xiao-Jie Zhang, Jie Yang, Xiu-Ju Luo, Jun Peng
Apoptosis and receptor-interacting protein kinase 1/3(RIPK1/3)-mediated necroptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. Emricasan is an inhibitor of caspases in clinical trials for liver diseases while ponatinib could be a potential inhibitor for RIPK1/3. This study aims to investigate the effect of emricasan and/or ponatinib on cerebral I/R injury and the underlying mechanisms. Firstly, we evaluated the status of apoptosis and necroposis in a rat model of cerebral I/R under different conditions, which showed noticeable apoptosis and necroptosis under condition of 2-h ischemia and 24-h reperfusion; next, the preventive or therapeutic effect of emricasan or ponatinib on cerebral I/R injury was tested...
November 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29101355/particles-of-different-sizes-and-shapes-induce-neutrophil-necroptosis-followed-by-the-release-of-neutrophil-extracellular-trap-like-chromatin
#15
Jyaysi Desai, Orestes Foresto-Neto, Mohsen Honarpisheh, Stefanie Steiger, Daigo Nakazawa, Bastian Popper, Eva Miriam Buhl, Peter Boor, Shrikant R Mulay, Hans-Joachim Anders
The human body is exposed to a wide range of particles of industrial, environmental or internal origin such as asbestos, alum, silica or crystals of urate, calcium phosphate, calcium oxalate, cystine or cholesterol. Phagocytic clearance of such particles involves neutrophils and macrophages. Here we report that neutrophils encountering such particles of diverse sizes and shapes undergo necrotic cell death, a process associated with the formation of neutrophil extracellular trap (NET)-like extracellular DNA...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079707/ceramide-nanoliposomes-as-a-mlkl-dependent-necroptosis-inducing-chemotherapeutic-reagent-in-ovarian-cancer
#16
Xuewei Zhang, Kazuyuki Kitatani, Masafumi Toyoshima, Masumi Ishibashi, Toshinori Usui, Junko Minato, Mahy Egiz, Shogo Shigeta, Todd Fox, Tye Deering, Mark Kester, Nobuo Yaegashi
Ceramides are bioactive lipids that mediate cell death in cancer cells and ceramide-based therapy is now being tested in dose-escalating phase 1 clinical trials as a cancer treatment. Multiple nanoscale delivery systems for ceramide have been proposed to overcome the inherent toxicities, poor pharmacokinetics and difficult biophysics associated with ceramide. Using the ceramide nanoliposomes (CNL) we now investigate the therapeutic efficacy and signaling mechanisms of this nanoscale delivery platform in refractory ovarian cancer...
October 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29078411/peli1-functions-as-a-dual-modulator-of-necroptosis-and-apoptosis-by-regulating-ubiquitination-of-ripk1-and-mrna-levels-of-c-flip
#17
Huibing Wang, Huyan Meng, Xingyan Li, Kezhou Zhu, Kangyun Dong, Adnan K Mookhtiar, Huiting Wei, Ying Li, Shao-Cong Sun, Junying Yuan
Apoptosis and necroptosis are two distinct cell death mechanisms that may be activated in cells on stimulation by TNFα. It is still unclear, however, how apoptosis and necroptosis may be differentially regulated. Here we screened for E3 ubiquitin ligases that could mediate necroptosis. We found that deficiency of Pellino 1 (PELI1), an E3 ubiquitin ligase, blocked necroptosis. We show that PELI1 mediates K63 ubiquitination on K115 of RIPK1 in a kinase-dependent manner during necroptosis. Ubiquitination of RIPK1 by PELI1 promotes the formation of necrosome and execution of necroptosis...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29078325/necroptosis-controls-net-generation-and-mediates-complement-activation-endothelial-damage-and-autoimmune-vasculitis
#18
Adrian Schreiber, Anthony Rousselle, Jan Ulrich Becker, Anne von Mässenhausen, Andreas Linkermann, Ralph Kettritz
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29076500/plasma-membrane-changes-during-programmed-cell-deaths
#19
REVIEW
Yingying Zhang, Xin Chen, Cyril Gueydan, Jiahuai Han
Ruptured and intact plasma membranes are classically considered as hallmarks of necrotic and apoptotic cell death, respectively. As such, apoptosis is usually considered a non-inflammatory process while necrosis triggers inflammation. Recent studies on necroptosis and pyroptosis, two types of programmed necrosis, revealed that plasma membrane rupture is mediated by MLKL channels during necroptosis but depends on non-selective gasdermin D (GSDMD) pores during pyroptosis. Importantly, the morphology of dying cells executed by MLKL channels can be distinguished from that executed by GSDMD pores...
October 27, 2017: Cell Research
https://www.readbyqxmd.com/read/29073079/inhibition-of-dai-dependent-necroptosis-by-the-z-dna-binding-domain-of-the-vaccinia-virus-innate-immune-evasion-protein-e3
#20
Heather Koehler, Samantha Cotsmire, Jeffrey Langland, Karen V Kibler, Daniel Kalman, Jason W Upton, Edward S Mocarski, Bertram L Jacobs
Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor, GSK872, and infection with this mutant virus led to phosphorylation and aggregation of MLKL, the executioner of necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
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