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https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#1
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28179994/matrine-induces-rip3-dependent-necroptosis-in-cholangiocarcinoma-cells
#2
Beibei Xu, Minying Xu, Yuan Tian, Qiang Yu, Yujie Zhao, Xiong Chen, Panying Mi, Hanwei Cao, Bing Zhang, Gang Song, Yan-Yan Zhan, Tianhui Hu
The development of acquired resistance to pro-apoptotic antitumor agents is a major impediment to the cure of cholangiocarcinoma (CCA). Antitumor drugs inducing non-apoptotic cell death are considered as a new approach to overcome such drug resistance. Here, we reported for the first time that matrine-induced necroptosis in CCA cell lines, differing from its classical role to induce apoptosis in many other kinds of cancer cells. CCA cells under matrine treatment exhibited typical necrosis-like but not apoptotic morphologic change...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28151480/ripk1-ripk3-promotes-vascular-permeability-to-allow-tumor-cell-extravasation-independent-of-its-necroptotic-function
#3
Kay Hänggi, Lazaros Vasilikos, Aida Freire Valls, Rosario Yerbes, Janin Knop, Lisanne M Spilgies, Kristy Rieck, Tvisha Misra, John Bertin, Peter J Gough, Thomas Schmidt, Carmen Ruiz de Almodòvar, W Wei-Lynn Wong
Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 1, 3 (RIPK1, RIPK3) and mixed lineage kinase domain-like protein (MLKL). The kinase of RIPK3 phosphorylates MLKL causing MLKL to form a pore-like structure, allowing intracellular contents to release and cell death to occur. Alternatively, RIPK1 and RIPK3 have been shown to regulate cytokine production directly influencing inflammatory immune infiltrates. Recent data suggest that necroptosis may contribute to the malignant transformation of tumor cells in vivo and we asked whether necroptosis may have a role in the tumor microenvironment altering the ability of the tumor to grow or metastasize...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28151467/augmented-trophoblast-cell-death-in-preeclampsia-can-proceed-via-ceramide-mediated-necroptosis
#4
Liane Jennifer Bailey, Sruthi Alahari, Andrea Tagliaferro, Martin Post, Isabella Caniggia
Preeclampsia, a serious hypertensive disorder of pregnancy, is characterized by elevated ceramide (CER) content that is responsible for heightened trophoblast cell death rates via apoptosis and autophagy. Whether trophoblast cells undergo necroptosis, a newly characterized form of regulated necrosis, and the potential role of CER in this process remain to be established. Herein, we report that exposure of both JEG3 cells and primary isolated cytotrophoblasts to C16:0 CER in conjunction with a caspase-8 inhibitor (Q-VD-OPh) promoted necroptotic cell death, as evidenced by increased expression and association of receptor-interacting protein kinases RIP1 and RIP3, as well as phosphorylation of mixed lineage kinase domain-like (MLKL) protein...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28130493/mlkl-activation-triggers-nlrp3-mediated-processing-and-release-of-il-1%C3%AE-independently-of-gasdermin-d
#5
Kimberley D Gutierrez, Michael A Davis, Brian P Daniels, Tayla M Olsen, Pooja Ralli-Jain, Stephen W G Tait, Michael Gale, Andrew Oberst
Necroptosis is a form of programmed cell death defined by activation of the kinase receptor interacting protein kinase 3 and its downstream effector, the pseudokinase mixed lineage kinase domain-like (MLKL). Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. In this study, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1β...
January 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28126382/complex-pathologic-roles-of-ripk1-and-ripk3-moving-beyond-necroptosis
#6
REVIEW
Kelby W Wegner, Danish Saleh, Alexei Degterev
A process of regulated necrosis, termed necroptosis, has been recognized as a major contributor to cell death and inflammation occurring under a wide range of pathologic settings. The core event in necroptosis is the formation of the detergent-insoluble 'necrosome' complex of homologous Ser/Thr kinases, receptor protein interacting kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3), which promotes phosphorylation of a key prodeath effector, mixed lineage kinase domain-like (MLKL), by RIPK3. Core necroptosis mediators are under multiple controls, which have been a subject of intense investigation...
January 23, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28125817/participation-of-necroptosis-in-the-host-response-to-acute-bacterial-pneumonia
#7
Danielle Ahn, Alice Prince
Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus, as well as the host-adapted pathogens responsible for health care-associated pneumonias, such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcecsens, are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages, and, in so doing, contribute to host pathology through the loss of their critical immunoregulatory functions...
January 27, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28106882/combination-of-iap-antagonist-and-ifn%C3%AE-activates-novel-caspase-10-and-ripk1-dependent-cell-death-pathways
#8
Maria C Tanzer, Nufail Khan, James A Rickard, Nima Etemadi, Najoua Lalaoui, Sukhdeep Kaur Spall, Joanne M Hildebrand, David Segal, Maria Miasari, Diep Chau, WendyWei-Lynn Wong, Mark McKinlay, Srinivas K Chunduru, Christopher A Benetatos, Stephen M Condon, James E Vince, Marco J Herold, John Silke
Peptido-mimetic inhibitor of apoptosis protein (IAP) antagonists (Smac mimetics (SMs)) can kill tumour cells by depleting endogenous IAPs and thereby inducing tumour necrosis factor (TNF) production. We found that interferon-γ (IFNγ) synergises with SMs to kill cancer cells independently of TNF- and other cell death receptor signalling pathways. Surprisingly, CRISPR/Cas9 HT29 cells doubly deficient for caspase-8 and the necroptotic pathway mediators RIPK3 or MLKL were still sensitive to IFNγ/SM-induced killing...
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28096356/active-mlkl-triggers-the-nlrp3-inflammasome-in-a-cell-intrinsic-manner
#9
Stephanie A Conos, Kaiwen W Chen, Dominic De Nardo, Hideki Hara, Lachlan Whitehead, Gabriel Núñez, Seth L Masters, James M Murphy, Kate Schroder, David L Vaux, Kate E Lawlor, Lisa M Lindqvist, James E Vince
Necroptosis is a physiological cell suicide mechanism initiated by receptor-interacting protein kinase-3 (RIPK3) phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which results in disruption of the plasma membrane. Necroptotic cell lysis, and resultant release of proinflammatory mediators, is thought to cause inflammation in necroptotic disease models. However, we previously showed that MLKL signaling can also promote inflammation by activating the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome to recruit the adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and trigger caspase-1 processing of the proinflammatory cytokine IL-1β...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28088644/tert-butyl-hydroperoxide-t-bhp-induced-apoptosis-and-necroptosis-in-endothelial-cells-roles-of-nox4-and-mitochondrion
#10
Wenwen Zhao, Haitao Feng, Wen Sun, Kang Liu, Jin-Jian Lu, Xiuping Chen
Oxidative stress causes endothelial death while underlying mechanisms remain elusive. Herein, the pro-death effect of tert-butyl hydroperoxide (t-BHP) was investigated with low concentration (50μM) of t-BHP (t-BHPL) and high concentration (500μM) of t-BHP (t-BHPH). Both t-BHPL and t-BHPH induced endothelial cell death was determined. T-BHPL induced caspase-dependent apoptosis and reactive oxygen species (ROS) generation, which was inhibited by N-acetyl-L-cysteine (NAC). Furthermore, NADPH oxidase inhibitor diphenyleneiodonium (DPI), NOX4 siRNA, and NOX4 inhibitor GKT137831 reduced t-BHPL-induced ROS generation while mitochondrial respiratory chain inhibitors rotenone (Rot), 2-thenoyltrifluoroacetone (TTFA), and antimycin A (AA) failed to do so...
January 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28069136/the-inflammatory-signal-adaptor-ripk3-functions-beyond-necroptosis
#11
K Moriwaki, F K-M Chan
Receptor interacting protein kinase 3 (RIPK3) is an essential serine/threonine kinase for necroptosis, a type of regulated necrosis. A variety of stimuli can cause RIPK3 activation through phosphorylation. Activated RIPK3 in turn phosphorylates and activates the downstream necroptosis executioner mixed lineage kinase domain-like (MLKL). Necroptosis is a highly inflammatory type of cell death because of the release of intracellular immunogenic contents from disrupted plasma membrane. Indeed, RIPK3-deficient mice exhibited reduced inflammation in many inflammatory disease models...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28065786/cisplatin-induced-necroptosis-in-tnf%C3%AE-dependent-and-independent-pathways
#12
Yanfang Xu, Hua-Bin Ma, Yu-Lu Fang, Zhi-Rong Zhang, Jing Shao, Mao Hong, Chao-Jun Huang, Jing Liu, Rui-Qing Chen
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28004006/the-different-effects-of-atorvastatin-and-pravastatin-on-cell-death-and-parp-activity-in-pancreatic-nit-1-cells
#13
Ya-Hui Chen, Yi-Chun Chen, Chin-San Liu, Ming-Chia Hsieh
Statins have been widely used drugs for lowering low-density lipoprotein and for preventing heart attack and stroke. However, the increased risk for developing diabetes during extended stain use and the molecular mechanisms remain unclear. The objective of this study was to elucidate the signaling pathway and biological function between necrosis and autophagy induced by atorvastatin (AS) and pravastatin (PS). Here we observed that atorvastatin (AS) can increase intracellular reactive oxygen species (ROS) and induce necrotic cell death and autophagy in NIT-1 cells, whereas pravastatin (PS) does not cause ROS and cell death but also induces autophagy...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27999438/necroptosis-in-development-inflammation-and-disease
#14
Ricardo Weinlich, Andrew Oberst, Helen M Beere, Douglas R Green
In the early 2000s, receptor-interacting serine/threonine protein kinase 1 (RIPK1), a molecule already recognized as an important regulator of cell survival, inflammation and disease, was attributed an additional function: the regulation of a novel cell death pathway that came to be known as necroptosis. Subsequently, the related kinase RIPK3 and its substrate mixed-lineage kinase domain-like protein (MLKL) were also implicated in the necroptotic pathway, and links between this pathway and apoptosis were established...
February 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27999433/insane-in-the-membrane-a-structural-perspective-of-mlkl-function-in-necroptosis
#15
REVIEW
Emma J Petrie, Joanne M Hildebrand, James M Murphy
Necroptosis (or 'programmed necrosis') is a caspase-independent cell death pathway that operates downstream of death receptors, including Tumour Necrosis Factor Receptor-1 (TNFR1), and the Toll-like receptors, TLR3 and TLR4. Owing to its immunogenicity, necroptosis has been attributed roles in the pathogenesis of several diseases, including inflammatory bowel disease and the tissue damage arising from ischaemic-reperfusion injuries. Only over the past 7 years has the core machinery of this pathway, the receptor-interacting protein kinase-3 (RIPK3) and the pseudokinase, Mixed Lineage Kinase domain-Like (MLKL), been defined...
January 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27978789/heat-shock-proteins-therapeutic-perspectives-in-inflammatory-disorders
#16
Rekha Khandia, Ashok K Munjal, Hafiz M N Iqbal, Kuldeep Dhama
Heat shock proteins (HSPs) are highly conserved proteins present in all kingdoms of organisms. These are expressed under stress conditions in order to protect the cells from injuries. The stress induced protein denaturation is rectified by refolding and remodelling. These are intracellular proteins but can be present in extracellular fluid like serum of the patients suffering from trauma, autoimmune and inflammatory disorders. Virtually in most inflammatory diseases, immune response towards HSPs is developed...
December 13, 2016: Recent Patents on Inflammation & Allergy Drug Discovery
https://www.readbyqxmd.com/read/27959630/necroptosis-mechanisms-and-relevance-to-disease
#17
Lorenzo Galluzzi, Oliver Kepp, Francis Ka-Ming Chan, Guido Kroemer
Necroptosis is a form of regulated cell death that critically depends on receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) and generally manifests with morphological features of necrosis. The molecular mechanisms that underlie distinct instances of necroptosis have just begun to emerge. Nonetheless, it has already been shown that necroptosis contributes to cellular demise in various pathophysiological conditions, including viral infection, acute kidney injury, and cardiac ischemia/reperfusion...
January 24, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#18
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27924226/questions-and-controversies-the-role-of-necroptosis-in-liver-disease
#19
REVIEW
Lily Dara, Zhang-Xu Liu, Neil Kaplowitz
Acute and chronic liver injury results in hepatocyte death and turnover. If injury becomes chronic, the continuous cell death and turnover leads to chronic inflammation, fibrosis and ultimately cirrhosis and hepatocellular carcinoma. Controlling liver cell death both in acute injury, to rescue the liver from acute liver failure, and in chronic injury, to curb secondary inflammation and fibrosis, is of paramount importance as a therapeutic strategy. Both apoptosis and necrosis occur in the liver, but the occurrence of necroptosis in the liver and its contribution to liver disease is controversial...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27920255/mlkl-channel-in-necroptosis-is-octamer-formed-by-tetramers-in-a-dyadic-process
#20
Deli Huang, Xinru Zheng, Zi-An Wang, Xin Chen, Wan-Ting He, Yingying Zhang, Jin-Gen Xu, Hang Zhao, Wenke Shi, Xin Wang, Yongqun Zhu, Jiahuai Han
Oligomerization of the mixed lineage kinase domain-like protein (MLKL) is essential for its cation channel function in necroptosis. Here we show that the MLKL channel is an octamer comprising of two previously identified tetramers most likely in their side-by-side position. Inter-molecule disulfide bonds are present in the tetramer but are not required for the octamer assembly and necroptosis. MLKL forms oligomers in the necrosome, and is then released from the necrosome before or during its membrane translocation...
December 5, 2016: Molecular and Cellular Biology
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