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https://www.readbyqxmd.com/read/28650960/phosphatidylserine-externalization-necroptotic-bodies-release-and-phagocytosis-during-necroptosis
#1
Sefi Zargarian, Inbar Shlomovitz, Ziv Erlich, Aria Hourizadeh, Yifat Ofir-Birin, Ben A Croker, Neta Regev-Rudzki, Liat Edry-Botzer, Motti Gerlic
Necroptosis is a regulated, nonapoptotic form of cell death initiated by receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL) proteins. It is considered to be a form of regulated necrosis, and, by lacking the "find me" and "eat me" signals that are a feature of apoptosis, necroptosis is considered to be inflammatory. One such "eat me" signal observed during apoptosis is the exposure of phosphatidylserine (PS) on the outer plasma membrane. Here, we demonstrate that necroptotic cells also expose PS after phosphorylated mixed lineage kinase-like (pMLKL) translocation to the membrane...
June 26, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28649853/cationic-liposome-co-encapsulation-of-smac-mimetic-and-zvad-using-a-novel-lipid-bilayer-fusion-loaded-with-mlkl-pdna-for-tumor-inhibition-in-vivo
#2
Dan Sun, Linshu Zhao, Junzhong Lin, Yun Zhao, Yu Zheng
The increase in multidrug resistance among colon cancer cells presents a challenge for the development of effective therapies. Small-molecule analogs of second mitochondria-derived activator of caspase (SMAC) mimetic in association with mixed lineage kinase domain-like protein (MLKL)-pDNA and z-VAD-fmk have shown ideal antitumor effects in colon cancer cells in vitro via induction of RIP3-dependent necroptosis. To achieve synergistic antitumor effects in vivo, liposomes loaded with SMAC mimetic, MLKL-pDNA and z-VAD-fmk have been developed using novel lipid fusion methods to co-localize the molecules of interest within the tumor cells...
June 26, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28593135/evaluation-of-cell-death-pathways-initiated-by-antitumor-drugs-melatonin-and-valproic-acid-in-bladder-cancer-cells
#3
Siwei Liu, Bilin Liang, Huiting Jia, Yuhan Jiao, Zhongqiu Pang, Yongye Huang
Effective drug combinations have the potential to strengthen therapeutic efficacy and combat drug resistance. Both melatonin and valproic acid (VPA) exhibit antitumor activities in various cancer cells. The aim of this study was to evaluate the cell death pathways initiated by anticancer combinatorial effects of melatonin and VPA in bladder cancer cells. The results demonstrated that the combination of melatonin and VPA leads to significant synergistic growth inhibition of UC3 bladder cancer cells. Gene expression studies revealed that cotreatment with melatonin and VPA triggered the up-regulation of certain genes related to apoptosis (TNFRSF10A and TNFRSF10B), autophagy (BECN, ATG3 and ATG5) and necrosis (MLKL, PARP-1 and RIPK1)...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28592284/biogenic-selenium-nanoparticles-induce-ros-mediated-necroptosis-in-pc-3-cancer-cells-through-tnf-activation
#4
Praveen Sonkusre, Swaranjit Singh Cameotra
BACKGROUND: Selenium is well documented to inhibit cancer at higher doses; however, the mechanism behind this inhibition varies widely depending on the cell type and selenium species. Previously, we have demonstrated that Bacillus licheniformis JS2 derived biogenic selenium nanoparticles (SeNPs) induce non-apoptotic cell death in prostate adenocarcinoma cell line, PC-3, at a minimal concentration of 2 µg Se/ml, without causing toxicity to the primary cells. However, the mechanism behind its anticancer activity was elusive...
June 7, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28591723/rip1-is-a-central-signaling-protein-in-regulation-of-tnf-%C3%AE-trail-mediated-apoptosis-and-necroptosis-during-newcastle-disease-virus-infection
#5
Ying Liao, Huaxia Wang, Xiang Mao, Hongjie Fang, Huang Wang, Yanrong Li, Yinjie Sun, Chun Meng, Lei Tan, Cuiping Song, Xusheng Qiu, Chan Ding
Newcastle disease virus (NDV) is an oncolytic virus which selectively replicates in tumor cells and exerts anti-tumor cytotoxic activity by promoting cell death. In this study, we focus on characterization of the underlying mechanisms of NDV-induced cell death in HeLa cells. We find that NDV Herts/33 strain triggers both extrinsic and intrinsic apoptosis at late infection times. The activation of NF-кB pathway and subsequent up-regulation of TNF-α/TRAIL initiates extrinsic apoptosis, leading to activation of caspase 8 and cleavage of Bid into tBid...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28574501/rip1-kinase-activity-dependent-roles-in-embryonic-development-of-fadd-deficient-mice
#6
Yongbo Liu, Cunxian Fan, Yifan Zhang, Xianjun Yu, Xiaoxia Wu, Xixi Zhang, Qun Zhao, Haiwei Zhang, Qun Xie, Ming Li, Xiaoming Li, Qiurong Ding, Hao Ying, Dali Li, Haibing Zhang
RIP1 is an essential regulator of TNF-induced signaling complexes mediating NF-κB activation, apoptosis and necroptosis. Loss of Rip1 rescues the embryonic lethality of Fadd or Caspase-8-deficient mice, even though the double knockout mice die shortly after birth like Rip1-deficient mice. Recent studies demonstrated that mice expressing RIP1 kinase-dead mutants developed normally and resisted necroptotic stimuli in vitro and in vivo. However, the impact of RIP1 kinase activity on Fadd(-/-) embryonic development remains unknown...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28572508/cardioprotective-role-of-traf2-by-suppressing-apoptosis-and-necroptosis
#7
Xiaoyun Guo, Haifeng Yin, Lei Li, Yi Chen, Jing Li, Jessica Doan, Rachel N Steinmetz, Qinghang Liu
Background -Programed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. Methods -We examined the role of Traf2 (TNF receptor-associated factor 2) in regulating myocardial necroptosis and remodeling using genetic mouse models...
June 1, 2017: Circulation
https://www.readbyqxmd.com/read/28556445/induction-of-necroptosis-in-cancer-stem-cells-by-a-nickel-ii-dithiocarbamate-phenanthroline-complex
#8
Marie Flamme, Paul Cressey, Chunxin Lu, Peter Bruno, Arvin Eskandari, Michael Hemann, Graeme Hogarth, Kogularamanan Suntharalingam
The cytotoxic properties of a series of nickel(II)-dithiocarbamate phenanthroline complexes is reported. The complexes, 1-6 kill bulk cancer cells and cancer stem cells (CSCs) with micromolar potency. Two of the complexes, 2 and 6 kill breast cancer stem cell (CSC)-enriched HMLER-shEcad cells 2-fold better than breast CSC-depleted HMLER cells. Complex 2 inhibits mammosphere formation to a better extent than salinomycin (a CSC-specific toxin). Detailed mechanistic studies suggest that 2 induces CSC death by necroptosis, a programmed form of necrosis...
May 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28551825/necroptosis-and-ferroptosis-are-alternative-cell-death-pathways-that-operate-in-acute-kidney-failure
#9
Tammo Müller, Christin Dewitz, Jessica Schmitz, Anna Sophia Schröder, Jan Hinrich Bräsen, Brent R Stockwell, James M Murphy, Ulrich Kunzendorf, Stefan Krautwald
Ferroptosis is a recently recognized caspase-independent form of regulated cell death that is characterized by the accumulation of lethal lipid ROS produced through iron-dependent lipid peroxidation. Considering that regulation of fatty acid metabolism is responsible for the membrane-resident pool of oxidizable fatty acids that undergo lipid peroxidation in ferroptotic processes, we examined the contribution of the key fatty acid metabolism enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), in regulating ferroptosis...
May 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28539327/quantitative-phospho-proteomic-analysis-of-tnf%C3%AE-nf%C3%AE%C2%BAb-signaling-reveals-a-role-for-ripk1-phosphorylation-in-suppressing-necrotic-cell-death
#10
Firaz Mohideen, Joao Paolo, Alban Ordureau, Steve P Gygi, J Wade Harper
TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα, and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level...
May 24, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#11
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28498367/initiation-and-execution-mechanisms-of-necroptosis-an-overview
#12
REVIEW
Sasker Grootjans, Tom Vanden Berghe, Peter Vandenabeele
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domain-like (MLKL)...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28473408/lysis-of-human-neutrophils-by-community-associated-methicillin-resistant-staphylococcus-aureus
#13
Mallary C Greenlee-Wacker, Silvie Kremserová, William M Nauseef
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes infections associated with extensive tissue damage and necrosis. In vitro, human neutrophils fed CA-MRSA lyse by an unknown mechanism that is inhibited by necrostatin-1, an allosteric inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK-1). RIPK-1 figures prominently in necroptosis, a specific form of programmed cell death dependent on RIPK-1, RIPK-3, and the mixed-lineage kinase-like protein (MLKL). We previously reported that necrostatin-1 inhibits lysis of human neutrophils fed CA-MRSA and attributed the process to necroptosis...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28472590/evidence-of-necroptosis-in-hearts-subjected-to-various-forms-of-ischemic-insults
#14
Adriana Adameova, Jaroslav Hrdlicka, Adrian Szobi, Veronika Farkasova, Katarina Kopaskova, Martina Murarikova, Jan Neckar, Frantisek Kolar, Tatiana Ravingerova, Naranjan S Dhalla
Long-lasting ischemia can result in cell loss; however, repeated episodes of brief ischemia increase the resistance of the heart against deleterious effects of subsequent prolonged ischemic insult and promote cell survival. Traditionally, it is believed that the supply of blood to the ischemic heart is associated with release of cytokines, activation of inflammatory response, and induction of necrotic cell death. In the past few years, this paradigm of passive necrosis as an uncontrolled cell death has been re-examined and the existence of a strictly regulated form of necrotic cell death, necroptosis, has been documented...
May 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28462531/the-interplay-of-ikk-nf-%C3%AE%C2%BAb-and-ripk1-signaling-in-the-regulation-of-cell-death-tissue-homeostasis-and-inflammation
#15
REVIEW
Vangelis Kondylis, Snehlata Kumari, Katerina Vlantis, Manolis Pasparakis
Regulated cell death pathways have important functions in host defense and tissue homeostasis. Studies in genetic mouse models provided evidence that cell death could cause inflammation in different tissues. Inhibition of RIPK3-MLKL-dependent necroptosis by FADD and caspase-8 was identified as a key mechanism preventing inflammation in epithelial barriers. Moreover, the interplay between IKK/NF-κB and RIPK1 signaling was recognized as a critical determinant of tissue homeostasis and inflammation. NEMO was shown to regulate RIPK1 kinase activity-mediated apoptosis by NF-κB-dependent and -independent functions, which are critical for averting chronic tissue injury and inflammation in the intestine and the liver...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28462528/the-in-vivo-evidence-for-regulated-necrosis
#16
REVIEW
Wulf Tonnus, Andreas Linkermann
Necrosis is a hallmark of several widespread diseases or their direct complications. In the past decade, we learned that necrosis can be a regulated process that is potentially druggable. RIPK3- and MLKL-mediated necroptosis represents by far the best studied pathway of regulated necrosis. During necroptosis, the release of damage-associated molecular patterns (DAMPs) drives a phenomenon referred to as necroinflammation, a common consequence of necrosis. However, most studies of regulated necrosis investigated cell lines in vitro in a cell autonomous manner, which represents a non-physiological situation...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28462524/ripk3-driven-cell-death-during-virus-infections
#17
REVIEW
Jason W Upton, Maria Shubina, Siddharth Balachandran
The programmed self-destruction of infected cells is a powerful antimicrobial strategy in metazoans. For decades, apoptosis represented the dominant mechanism by which the virus-infected cell was thought to undergo programmed cell death. More recently, however, new mechanisms of cell death have been described that are also key to host defense. One such mechanism in vertebrates is programmed necrosis, or "necroptosis", driven by receptor-interacting protein kinase 3 (RIPK3). Once activated by innate immune stimuli, including virus infections, RIPK3 phosphorylates the mixed lineage kinase domain-like protein (MLKL), which then disrupts cellular membranes to effect necroptosis...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28461567/kinase-activities-of-ripk1-and-ripk3-can-direct-ifn-%C3%AE-synthesis-induced-by-lipopolysaccharide
#18
Danish Saleh, Malek Najjar, Matija Zelic, Saumil Shah, Shoko Nogusa, Apostolos Polykratis, Michelle K Paczosa, Peter J Gough, John Bertin, Michael Whalen, Katherine A Fitzgerald, Nikolai Slavov, Manolis Pasparakis, Siddharth Balachandran, Michelle Kelliher, Joan Mecsas, Alexei Degterev
The innate immune response is a central element of the initial defense against bacterial and viral pathogens. Macrophages are key innate immune cells that upon encountering pathogen-associated molecular patterns respond by producing cytokines, including IFN-β. In this study, we identify a novel role for RIPK1 and RIPK3, a pair of homologous serine/threonine kinases previously implicated in the regulation of necroptosis and pathologic tissue injury, in directing IFN-β production in macrophages. Using genetic and pharmacologic tools, we show that catalytic activity of RIPK1 directs IFN-β synthesis induced by LPS in mice...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28456683/patchouli-alcohol-ameliorates-dextran-sodium-sulfate-induced-experimental-colitis-and-suppresses-tryptophan-catabolism
#19
Chang Qu, Zhong-Wen Yuan, Xiu-Ting Yu, Yan-Feng Huang, Guang-Hua Yang, Jian-Nan Chen, Xiao-Ping Lai, Zi-Ren Su, Hui-Fang Zeng, Ying Xie, Xiao-Jun Zhang
Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days...
April 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28454582/analysis-of-necroptotic-proteins-in-failing-human-hearts
#20
Adrián Szobi, Eva Gonçalvesová, Zoltán Varga, Przemyslaw Leszek, Mariusz Kuśmierczyk, Michal Hulman, Ján Kyselovič, Péter Ferdinandy, Adriana Adameová
BACKGROUND: Cell loss and subsequent deterioration of contractile function are hallmarks of chronic heart failure (HF). While apoptosis has been investigated as a participant in the progression of HF, it is unlikely that it accounts for the total amount of non-functional tissue. In addition, there is evidence for the presence of necrotic cardiomyocytes in HF. Therefore, the objective of this study was to investigate the necroptotic proteins regulating necroptosis, a form of programmed necrosis, and thereby assess its potential role in human end-stage HF...
April 28, 2017: Journal of Translational Medicine
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