keyword
MENU ▼
Read by QxMD icon Read
search

RIPK3

keyword
https://www.readbyqxmd.com/read/28715128/sibiriline-a-new-small-chemical-inhibitor-of-receptor-interacting-protein-kinase-1-prevents-immune-dependent-hepatitis
#1
Fabienne Le Cann, Claire Delehouzé, Sabrina Penna-Leverrier, Aveline Filliol, Arnaud Comte, Olivier Delalande, Nathalie Desban, Blandine Baratte, Isabelle Gallais, Claire Piquet-Pellorce, Florence Faurez, Marion Bonnet, Yvette Mettey, Peter Goekjian, Michel Samson, Peter Vandenabeele, Stéphane Bach, Marie-Thérèse Dimanche-Boitrel
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-Interacting Protein Kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a non-commercial kinase-focused chemical library allowed us to identify Sibiriline as new inhibitor of necroptosis induced by TNF in Fas-Associated protein with Death Domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis...
July 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28686578/culling-of-apcs-by-inflammatory-cell-death-pathways-restricts-tim3-and-pd-1-expression-and-promotes-the-survival-of-primed-cd8-t-cells
#2
Rajen Patel, Kwangsin Kim, Bojan Shutinoski, Kristina Wachholz, Lakshmi Krishnan, Subash Sad
We evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8(+) T-cell priming during infection of mice with Salmonella typhimurium (ST). Our results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8(+) T cells. However, the maintenance of primed CD8(+) T cells was greatly compromised when both these pathways were disabled. Caspase-1- and RipK3-signaling did not influence NF-κB signaling in APCs, but synergized to promote processing of IL-1 and IL-18...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28676433/the-neurotoxicant-pcb-95-by-increasing-the-neuronal-transcriptional-repressor-rest-down-regulates-caspase-8-and-increases-ripk1-ripk3-and-mlkl-expression-determining-necroptotic-neuronal-death
#3
Natascia Guida, Giusy Laudati, Angelo Serani, Luigi Mascolo, Pasquale Molinaro, Paolo Montuori, Gianfranco Di Renzo, Lorella Mt Canzoniero, Luigi Formisano
Our previous study showed that the environmental neurotoxicant non-dioxin-like polychlorinated biphenyl (PCB)-95 increases RE1-Silencing Transcription Factor (REST) expression, which is related to necrosis, but not apoptosis, of neurons. Meanwhile, necroptosis is a type of a programmed necrosis that is positively regulated by receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like (MLKL) and negatively regulated by caspase-8. Here we evaluated whether necroptosis contributes to PCB-95-induced neuronal death through REST up-regulation...
July 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28666573/mlkl-the-protein-that-mediates-necroptosis-also-regulates-endosomal-trafficking-and-extracellular-vesicle-generation
#4
Seongmin Yoon, Andrew Kovalenko, Konstantin Bogdanov, David Wallach
Activation of the pseudokinase mixed lineage kinase domain-like (MLKL) upon its phosphorylation by the protein kinase RIPK3 triggers necroptosis, a form of programmed cell death in which rupture of cellular membranes yields release of intracellular components. We report that MLKL also associated with endosomes and controlled the transport of endocytosed proteins, thereby enhancing degradation of receptors and ligands, modulating their induced signaling and facilitating the generation of extracellular vesicles...
June 22, 2017: Immunity
https://www.readbyqxmd.com/read/28661484/sorafenib-tosylate-inhibits-directly-necrosome-complex-formation-and-protects-in-mouse-models-of-inflammation-and-tissue-injury
#5
Sofie Martens, Manhyung Jeong, Wulf Tonnus, Friederike Feldmann, Sam Hofmans, Vera Goossens, Nozomi Takahashi, Jan Hinrich Bräsen, Eun-Woo Lee, Pieter Van der Veken, Jurgen Joossens, Koen Augustyns, Simone Fulda, Andreas Linkermann, Jaewhan Song, Peter Vandenabeele
Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation of the receptor-interacting protein kinases 1 and 3 (RIPK1/3) in a necrosome complex, eventually leading to the phosphorylation and relocation of mixed lineage kinase domain like protein (MLKL). Using a high-content screening of small compounds and FDA-approved drug libraries, we identified the anti-cancer drug Sorafenib tosylate as a potent inhibitor of TNF-dependent necroptosis...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28650960/phosphatidylserine-externalization-necroptotic-bodies-release-and-phagocytosis-during-necroptosis
#6
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 2017: PLoS Biology
https://www.readbyqxmd.com/read/28592892/noncanocial-cell-death-program-independent-of-caspase-activation-cascade-and-necroptotic-modules-is-elicited-by-loss-of-tgf%C3%AE-activated-kinase-1
#7
September R Mihaly, Yosuke Sakamachi, Jun Ninomiya-Tsuji, Sho Morioka
Programmed cell death (PCD) occurs in several forms including apoptosis and necroptosis. Apoptosis is executed by the activation of caspases, while necroptosis is dependent on the receptor interacting protein kinase 3 (RIPK3). Precise control of cell death is crucial for tissue homeostasis. Indeed, necroptosis is triggered by caspase inhibition to ensure cell death. Here we identified a previously uncharacterized cell death pathway regulated by TAK1, which is unexpectedly provoked by inhibition of caspase activity and necroptosis cascades...
June 7, 2017: Scientific Reports
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
#8
Firaz Mohideen, Joao A Paulo, 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...
July 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28524164/ripped-for-neuroinflammation
#9
Bart Tummers, Douglas R Green
Activation of the receptor interacting serine/threonine kinase (RIPK) 3 mediates an inflammatory type of cell death called necroptosis; in addition, RIPK3 has necroptosis-independent roles in inflammation, although these are not well defined. In a recent study published in Cell, Daniels and colleagues demonstrate that RIPK3 controls West Nile virus infection by promoting neuroinflammation in the central nervous system without affecting neuronal death.
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28511054/synthesis-and-in-vitro-anticancer-activity-of-new-2-thioxo-oxazolidin-4-one-derivatives
#10
Júlia Furtado Campos, Michelly Cristiny Pereira, Wanessa Layssa Batista de Sena, Caio Gomes de Barros Martins, Jamerson Ferreira de Oliveira, Cezar Augusto da Cruz Amorim, Moacyr Jesus Barreto de Melo Rêgo, Marina Galdino da Rocha Pitta, Maria do Carmo Alves de Lima, Maira Galdino da Rocha Pitta, Ivan da Rocha Pitta
BACKGROUND: Oxazolidinones derivatives exhibit different biological properties, including anticancer activity. This work aimed to investigate the anticancer potential of five novel 2-Thioxo-oxazolidin-4-one derivatives. METHODS: Cytotoxicity assays were performed in human peripheral blood mononuclear cells (PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection and cell cycle were evaluated by flow cytometry and the expression of genes involved in cell death processes by Real-Time PCR...
March 18, 2017: Pharmacological Reports: PR
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/28462531/the-interplay-of-ikk-nf-%C3%AE%C2%BAb-and-ripk1-signaling-in-the-regulation-of-cell-death-tissue-homeostasis-and-inflammation
#13
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
#14
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
#15
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/28462521/ripk3-in-cell-death-and-inflammation-the-good-the-bad-and-the-ugly
#16
REVIEW
Susana Orozco, Andrew Oberst
Necroptosis is a form of cell death that can be observed downstream of death receptor or pattern recognition receptor signaling under certain cellular contexts, or in response to some viral and bacterial infections. The receptor interacting protein kinases-1 (RIPK1) and RIPK3 are at the core of necroptotic signaling, among other proteins. Because this pathway is normally halted by the pro-apoptotic protease caspase-8 and the IAP ubiquitin ligases, how and when necroptosis is triggered in physiological settings are ongoing questions...
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
#17
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/28451648/necroptosis-and-cancer
#18
Ayaz Najafov, Hongbo Chen, Junying Yuan
Necroptosis is a programmed lytic cell death pathway, deregulation of which is linked to various inflammatory disorders. Escape from programmed cell death and inflammation play a significant role in cancer, and therefore, investigating the role of necroptosis in cancer has been of high interest. Necroptosis has been shown to promote cancer metastasis and T cells death. Escape from necroptosis via loss of RIPK3 expression is a feature of some cancers. While necroptosis is a promising novel target for cancer therapies, further investigation into its biological role in carcinogenesis is warranted...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28445730/ripk3-mediates-necroptosis-during-embryonic-development-and-postnatal-inflammation-in-fadd-deficient-mice
#19
Qun Zhao, XianJun Yu, HaiWei Zhang, YongBo Liu, XiXi Zhang, XiaoXia Wu, Qun Xie, Ming Li, Hao Ying, Haibing Zhang
RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase domain (Ripk3(Δ/Δ) mice), thus abolishing its kinase activity. Ripk3(Δ/Δ) cells were resistant to necroptosis stimulation in vitro, and Ripk3(Δ/Δ) mice were protected from necroptotic diseases...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28428949/p2x1-p2x4-and-p2x7-receptor-knock-out-mice-expose-differential-outcome-of-sepsis-induced-by-%C3%AE-haemolysin-producing-escherichia-coli
#20
Anne-Sofie Greve, Marianne Skals, Steen K Fagerberg, Wulf Tonnus, Svend Ellermann-Eriksen, Richard J Evans, Andreas Linkermann, Helle A Praetorius
α-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis. Since free hemoglobin in the blood is known to be associated with a worse outcome in sepsis one could speculate that inhibition of P2X receptors would ameliorate the course of sepsis...
2017: Frontiers in Cellular and Infection Microbiology
keyword
keyword
37620
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"