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https://www.readbyqxmd.com/read/29042502/lipopolysaccharide-from-crypt-specific-core-microbiota-modulates-the-colonic-epithelial-proliferation-to-differentiation-balance
#1
Tomoaki Naito, Céline Mulet, Cristina De Castro, Antonio Molinaro, Azadeh Saffarian, Giulia Nigro, Marion Bérard, Mélanie Clerc, Amy B Pedersen, Philippe J Sansonetti, Thierry Pédron
We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29018243/6e11-a-highly-selective-inhibitor-of-receptor-interacting-protein-kinase-1-protects-cells-against-cold-hypoxia-reoxygenation-injury
#2
C Delehouzé, S Leverrier-Penna, F Le Cann, A Comte, M Jacquard-Fevai, O Delalande, N Desban, B Baratte, I Gallais, F Faurez, M C Bonnet, M Hauteville, P G Goekjian, R Thuillier, F Favreau, P Vandenabeele, T Hauet, M T Dimanche-Boitrel, S Bach
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28994372/-clarifying-the-role-of-ripk3-and-necroptosis-in-non-alcoholic-steatohepatitis
#3
Jérémie Gautheron
No abstract text is available yet for this article.
October 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28993192/up-regulation-of-rip3-alleviates-cervical-cancer-progression-through-inducing-necroptosis
#4
Dong-Li Zhang, Gui-Xia Sun, Jun Tian, Hong-Xia Zhang
Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an important part of the cellular machinery, executing programmed necroptosis. However, the biological role and clinical significance of RIP3 in cervical cancer remains to be further elucidated. Here, we reported that RIP3 was expressed lowly in cervical cancer cell lines and clinical cervical tumor samples, along with the reduction of receptor-interacting protein 1 (RIP1) and p-mixed lineage kinase domain-like protein (MLKL). Further, we found that over-expressing RIP3 suppressed the proliferation and tumorigenicity of cervical cancer cells both in vitro and in vivo...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28978351/the-caspase-8-ripk3-signaling-axis-in-antigen-presenting-cells-controls-the-inflammatory-arthritic-response
#5
Salina Dominguez, Anna B Montgomery, G Kenneth Haines, Christina L Bloomfield, Carla M Cuda
BACKGROUND: Caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, but maintains functions beyond cell death that involve suppression of receptor-interacting serine-threonine kinases (RIPKs). A genome-wide association study meta-analysis revealed an SNP associated with risk of rheumatoid arthritis (RA) development within the locus containing the gene encoding for caspase-8. Innate immune cells, like macrophages and dendritic cells, are gaining momentum as facilitators of autoimmune disease pathogenesis, and, in particular, RA...
October 4, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28975372/t-buooh-induces-ferroptosis-in-human-and-murine-cell-lines
#6
Christine Wenz, Dagmar Faust, Berenike Linz, Christian Turmann, Teodora Nikolova, John Bertin, Peter Gough, Peter Wipf, Anna Sophia Schröder, Stefan Krautwald, Cornelia Dietrich
Reactive oxygen species (ROS)-induced apoptosis has been extensively studied. Increasing evidence suggests that ROS, for instance, induced by hydrogen peroxide (H2O2), might also trigger regulated necrotic cell death pathways. Almost nothing is known about the cell death pathways triggered by tertiary-butyl hydroperoxide (t-BuOOH), a widely used inducer of oxidative stress. The lipid peroxidation products induced by t-BuOOH are involved in the pathophysiology of many diseases, such as cancer, cardiovascular diseases, or diabetes...
October 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28933271/targeting-cell-necroptosis-and-apoptosis-induced-by-shikonin-via-receptor-interacting-protein-kinases-in-estrogen-receptor-positive-breast-cancer-cell-line-mcf-7
#7
Zahra Shahsavari, Fatemeh Karami-Tehrani, Siamak Salami
Recognition of a new therapeutic agent may activate an alternative programmed cell death for the treatment of breast cancer. Here, it has been tried to evaluate the effects of Shikonin, a naphthoquinone derivative of Lithospermum erythrorhizon, on the induction of necroptosis and apoptosis mediated by RIPK1-RIPK3 in the ER+ breast cancer cell line, MCF-7. In the current study, cell death modalities, cell cycle patterns, RIPK1 and RIPK3 expressions, caspase-3 and caspase-8 activities, reactive oxygen species and mitochondrial membrane potential have been evaluated in the Shikonin-treated MCF-7 cells...
September 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28919893/ripk3-fas-associated-death-domain-axis-regulates-pulmonary-immunopathology-to-cryptococcal-infection-independent-of-necroptosis
#8
Zhenzong Fa, Qun Xie, Wei Fang, Haibing Zhang, Haiwei Zhang, Jintao Xu, Weihua Pan, Jinhua Xu, Michal A Olszewski, Xiaoming Deng, Wanqing Liao
Fas-associated death domain (FADD) and receptor interacting protein kinase 3 (RIPK3) are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28892415/susceptibility-of-m-tuberculosis-infected-host-cells-to-phospho-mlkl-driven-necroptosis-is-dependent-on-cell-type-and-presence-of-tnf%C3%AE
#9
Rachel E Butler, Nitya Krishnan, Waldo Garcia-Jimenez, Robert Francis, Abbe Martyn, Tom Mendum, Shaza Felemban, Nicolas Locker, Javier Salguero-Bodes, Brian Robertson, Graham R Stewart
An important feature of Mycobacterium tuberculosis pathogenesis is the ability to control cell death in infected host cells, including inhibition of apoptosis and stimulation of necrosis. Recently an alternative form of programmed cell death, necroptosis, has been described where necrotic cell death is induced by apoptotic stimuli under conditions where apoptotic execution is inhibited. We show for the first time that M. tuberculosis and TNFα synergise to induce necroptosis in murine fibroblasts via RIPK1-dependent mechanisms and characterized by phosphorylation of Ser345 of the MLKL necroptosis death effector...
September 11, 2017: Virulence
https://www.readbyqxmd.com/read/28878015/thioredoxin-1-actively-maintains-the-pseudokinase-mlkl-in-a-reduced-state-to-suppress-disulfide-bond-dependent-mlkl-polymer-formation-and-necroptosis
#10
Eduardo Reynoso, Hua Liu, Lin Li, Anthony L Yuan, She Chen, Zhigao Wang
Necroptosis is an immunogenic cell death program that is associated with a host of human diseases, including inflammation, infections and cancer. Receptor-interacting protein kinase 3 (RIPK3) and its substrate mixed lineage kinase domain-like protein (MLKL) are required for necroptosis activation. Specifically, RIPK3-dependent MLKL phosphorylation promotes the assembly of disulfide bond-dependent MLKL polymers that drive the execution of necroptosis. However, how MLKL disulfide bond formation is regulated is not clear...
September 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28860618/interferon-gamma-regulates-inflammatory-cell-death-by-targeting-necroptosis-in-experimental-autoimmune-arthritis
#11
Seung Hoon Lee, Ji Ye Kwon, Se-Young Kim, KyoungAh Jung, Mi-La Cho
Interferon γ (IFN-γ) induces an inflammatory response and apoptotic cell death. Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with increased levels of inflammatory mediators, including tumour necrosis factor α (TNF-α) and T helper (Th) 17 cells, and downregulation of apoptosis of inflammatory cells. We hypothesized that IFN-γ would reduce inflammatory cell death in vitro and that loss of IFN-γ would aggravate inflammation in vivo. IFN-γ downregulated necroptosis and the expression of cellular FLICE-like inhibitory protein (cFLIPL) and mixed lineage kinase domain-like (MLKL)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854080/biological-events-and-molecular-signaling-following-mlkl-activation-during-necroptosis
#12
Yi-Nan Gong, Cliff Guy, Jeremy Chase Crawford, Douglas R Green
Necroptosis is a form of programmed necrotic cell death mediated by the kinase RIPK3 and its substrate MLKL. MLKL, which displays plasma membrane (PM) pore-forming activity upon phosphorylation, functions as the executioner during necroptosis. Thus, it was previously assumed that MLKL phosphorylation is the endpoint of the necroptotic signaling pathway. Here, we summarize several events that characterize the dying necroptotic cells after MLKL phosphorylation, including Ca(2+) influx, phosphatidylserine (PS) externalization, PM repair by ESCRT-III activation, and the final compromise of PM integrity...
October 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28842570/regulation-of-ripk1-activation-by-tak1-mediated-phosphorylation-dictates-apoptosis-and-necroptosis
#13
Jiefei Geng, Yasushi Ito, Linyu Shi, Palak Amin, Jiachen Chu, Amanda Tomie Ouchida, Adnan Kasim Mookhtiar, Heng Zhao, Daichao Xu, Bing Shan, Ayaz Najafov, Guangping Gao, Shizuo Akira, Junying Yuan
Stimulation of TNFR1 by TNFα can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear. Here, we report that TNFα-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 plays a key role in regulating this critical decision. Using phospho-Ser321 as a marker, we show that the transient phosphorylation of RIPK1 intermediate domain induced by TNFα leads to RIPK1-independent apoptosis when NF-κB activation is inhibited by cycloheximide...
August 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28842469/a20-restrains-thymic-regulatory-t-cell-development
#14
Julius Clemens Fischer, Vera Otten, Maike Kober, Christoph Drees, Marc Rosenbaum, Martina Schmickl, Simon Heidegger, Rudi Beyaert, Geert van Loo, Xian Chang Li, Christian Peschel, Marc Schmidt-Supprian, Tobias Haas, Silvia Spoerl, Hendrik Poeck
Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in myeloid cells and B cells. In naive CD4(+) T cells, A20 prevents kinase RIPK3-dependent necroptosis. Using mice deficient for A20 in T lineage cells, we show that thymic and peripheral Treg cell compartments are quantitatively enlarged because of a cell-intrinsic developmental advantage of A20-deficient thymic Treg differentiation...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28827318/mlkl-forms-disulfide-bond-dependent-amyloid-like-polymers-to-induce-necroptosis
#15
Shuzhen Liu, Hua Liu, Andrea Johnston, Sarah Hanna-Addams, Eduardo Reynoso, Yougui Xiang, Zhigao Wang
Mixed-lineage kinase domain-like protein (MLKL) is essential for TNF-α-induced necroptosis. How MLKL promotes cell death is still under debate. Here we report that MLKL forms SDS-resistant, disulfide bond-dependent polymers during necroptosis in both human and mouse cells. MLKL polymers are independent of receptor-interacting protein kinase 1 and 3 (RIPK1/RIPK3) fibers. Large MLKL polymers are more than 2 million Da and are resistant to proteinase K digestion. MLKL polymers are fibers 5 nm in diameter under electron microscopy...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28814095/quercetin-induces-apoptosis-and-necroptosis-in-mcf-7-breast-cancer-cells
#16
L Khorsandi, M Orazizadeh, F Niazvand, M R Abbaspour, E Mansouri, A Khodadadi
OBJECTIVE: This study investigated the quercetin (Que) effects on growth of MCF-7 human cancer breast cell line and its cellular death mechanism. BACKGROUND: Quercetin has been found to be very efficacious against many different types of cancer cells. However, the study is not sufficiently powered to demonastrate anticancer mechanisms. METHODS: MCF-7cells were treated by 50 µM/ ml of Que for 48 hours. MCF-7 cells were also pretreated with 10 Μm ZVAD (apoptosis inhibitor) or 3 mM Nec-1 (necroptosis inhibitor) for evaluation of cell death induced by apoptosis or necroptosis...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28810529/silymarin-induces-a-multi-targeted-cell-death-process-in-the-human-colon-cancer-cell-line-ht-29
#17
L Khorsandi, G Saki, N Bavarsad, M Mombeini
This study investigated the Silymarin (SM) effects on growth of HT-29 human colon cancer cell line and its cellular death mechanism. HT-29 cells were treated by 25μM/ml of SM for 48h. HT-29 cells were also pretreated with 10mmol zVAD (apoptosis inhibitor), 10mmol 3-MA (autophagy inhibitor) and 3mmol Nec (necroptosis inhibitor) for evaluation cell death induced by apoptosis, outophagy and necroptosis. MTT and clonogenicity assays revealed that the SM without inhibitors induced a significant decrease in cell viability and proliferation of HT-29 cells (p<0...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28807105/ripk1-ripk3-mlkl-dependent-necrosis-promotes-the-aging-of-mouse-male-reproductive-system
#18
Dianrong Li, Lingjun Meng, Tao Xu, Yaning Su, Xiao Liu, Zhiyuan Zhang, Xiaodong Wang
A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis. We report here that male reproductive organs of both Ripk3- and Mlkl-knockout mice retain 'youthful' morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. The RIPK3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild-type mice...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28783694/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#19
Teneema Kuriakose, Si Ming Man, R K Subbarao Malireddi, Rajendra Karki, Sannula Kesavardhana, David E Place, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
The interferon (IFN)-inducible protein Z-DNA binding protein 1 [ZBP1; also known as DNA-dependent activator of IFN regulatory factors (DAI) and DLM-1] was identified as a double-stranded DNA sensor, which instigates innate immune responses. However, this classification has been disputed, and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptor-interacting protein kinase 1 (RIPK1)-RIPK3-caspase-8 axis...
August 12, 2016: Science Immunology
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in%C3%A2-pancreatic%C3%A2-carcinoma
#20
Yangchun Xie, Shan Zhu, Meizuo Zhong, Manhua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of nonapoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
July 29, 2017: Gastroenterology
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