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RIP3 or RIPK3

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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/29331417/down-regulation-of-rip3-potentiates-cisplatin-chemoresistance-by-triggering-hsp90-erk-pathway-mediated-dna-repair-in-esophageal-squamous-cell-carcinoma
#2
Yulin Sun, Linhui Zhai, Shouzhi Ma, Chengpu Zhang, Lina Zhao, Ning Li, Yang Xu, Tao Zhang, Zhimin Guo, Heng Zhang, Ping Xu, Xiaohang Zhao
Receptor interacting protein kinase 3 (RIP3) is a critical regulator of programmed necrotic cell death. Here, we observed that RIP3 was significantly down-regulated in esophageal cancer. And its remaining expression was associated with better response to chemotherapy and prolonged survival. Notably, re-expression of kinase-dead RIP3 also restored cisplatin sensitivity, suggesting that some roles of RIP3 beyond necroptosis may be involved in cisplatin-based chemosensitivity. To investigate the mechanisms, a large-scale quantitative proteomics study was performed after cisplatin treatment in RIP3-knockdown cells...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330116/tnf-%C3%AE-increases-staphylococcus-aureus-induced-death-of-human-alveolar-epithelial-cell-line-a549-associated-with-rip3-mediated-necroptosis
#3
Shun-Hang Wen, Luo-Na Lin, Hu-Jun Wu, Lu Yu, Li Lin, Li-Li Zhu, Hai-Yan Li, Hai-Lin Zhang, Chang-Chong Li
AIM: To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN METHODS: The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus, where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses...
January 9, 2018: Life Sciences
https://www.readbyqxmd.com/read/29313217/temporal-pattern-and-crosstalk-of-necroptosis-markers-with-autophagy-and-apoptosis-associated-proteins-in-ischemic-hippocampus
#4
Fari Ryan, Fariba Khodagholi, Leila Dargahi, Dariush Minai-Tehrani, Abolhassan Ahmadiani
Necroptosis, a novel type of programmed cell death, has been recently implicated as a possible mechanism for cerebral ischemia-reperfusion (I/R) injury. We herein studied time-dependent changes of necroptosis markers along with apoptosis- and autophagy-associated proteins in rat hippocampus at 1, 3, 6, 12, 24, and 48 h after global cerebral I/R injury. Furthermore, to determine the cross talk between autophagy and necroptosis, we examined the effects of pretreatment with bafilomycin-A1 (Baf-A1), as a late-stage autophagy inhibitor, on necroptosis...
January 8, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29299822/necrostatin-1-protects-against-paraquat-induced-cardiac-contractile-dysfunction-via-rip1-rip3-mlkl-dependent-necroptosis-pathway
#5
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/29286079/exogenous-hydrogen-sulfide-protects-human-umbilical-vein-endothelial-cells-against-high-glucose%C3%A2-induced-injury-by-inhibiting-the-necroptosis-pathway
#6
Jiaqiong Lin, Meiji Chen, Donghong Liu, Ruixian Guo, Kai Lin, Haiou Deng, Ximei Zhi, Weijie Zhang, Jianqiang Feng, Wen Wu
Hyperglycemia is a key factor in the development of diabetic complications, including the processes of atherosclerosis. Receptor‑interacting protein 3 (RIP3), a mediator of necroptosis, is implicated in atherosclerosis development. Additionally, hydrogen sulfide (H2S) protects the vascular endothelium against hyperglycemia‑induced injury and attenuates atherosclerosis. On the basis of these findings, the present study aimed to confirm the hypothesis that necroptosis mediates high glucose (HG)‑induced injury in human umbilical vein endothelial cells (HUVECs), and that the inhibition of necroptosis contributes to the protective effect of exogenous H2S against this injury...
December 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29258580/apoptosis-and-necroptosis-of-mouse-hippocampal-and-parenchymal-astrocytes-microglia-and-neurons-caused-by-angiostrongylus-cantonensis-infection
#7
Zhang Mengying, Xu Yiyue, Pan Tong, Hu Yue, Yanin Limpanont, Huang Ping, Kamolnetr Okanurak, Wu Yanqi, Paron Dekumyoy, Zhou Hongli, Dorn Watthanakulpanich, Wu Zhongdao, Wang Zhi, Lv Zhiyue
BACKGROUND: Angiostrongylus cantonensis has been the only parasite among Angiostrongylidae to cause human central nervous system infection characterized by eosinophilic meningitis or meningoencephalitis. The mechanism of the extensive neurological impairments of hosts caused by A. cantonensis larvae remains unclear. The aim of the present study was to investigate apoptosis, necroptosis and autophagy in the brains of mice infected with A. cantonensis, which will be valuable for better understanding the pathogenesis of angiostrongyliasis cantonensis...
December 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29248830/mir-200a-5p-regulates-myocardial-necroptosis-induced-by-se-deficiency-via-targeting-rnf11
#8
Tianshu Yang, Changyu Cao, Jie Yang, Tianqi Liu, Xin Gen Lei, Ziwei Zhang, Shiwen Xu
Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue, we selected miR-200a-5p and its target gene ring finger protein 11 (RNF11) based on differential expression in cardiac tissue and confirmed the relationship between miR-200a-5p and RNF11 by dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR) in cardiomyocytes...
December 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#9
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/29248164/deficiency-of-receptor-interacting-protein-kinase-3-ripk3-attenuates-inflammation-and-organ-injury-in-neonatal-sepsis
#10
Laura W Hansen, Asha Jacob, Weng Lang Yang, Alexandra C Bolognese, Jose Prince, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
INTRODUCTION: Sepsis is the third leading cause of morbidity and mortality in neonates. Sepsis in neonates is characterized as the systemic inflammation owing to infection within the first 28days after birth. The molecular mechanism causing the exaggerated inflammation phenotype in neonates has not been completely elucidated. Receptor interacting protein kinase 3 (RIPK3) is a protein identified as a mediator in programmed necrosis or necroptosis. We hypothesize that RIPK3 could be responsible for the inflammatory response in neonates and that deficiency in the RIPK3 protein attenuates inflammation and organ injury in neonatal sepsis...
November 23, 2017: Journal of Pediatric Surgery
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
#11
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
#12
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/29225581/protective-effect-of-unacylated-ghrelin-on-compression-induced-skeletal-muscle-injury-mediated-by-sirt1-signaling
#13
Felix N Ugwu, Angus P Yu, Thomas K Sin, Bjorn T Tam, Christopher W Lai, S C Wong, Parco M Siu
Unacylated ghrelin, the predominant form of circulating ghrelin, protects myotubes from cell death, which is a known attribute of pressure ulcers. In this study, we investigated whether unacylated ghrelin protects skeletal muscle from pressure-induced deep tissue injury by abolishing necroptosis and apoptosis signaling and whether these effects were mediated by SIRT1 pathway. Fifteen adult Sprague Dawley rats were assigned to receive saline or unacylated ghrelin with or without EX527 (a SIRT1 inhibitor). Animals underwent two 6-h compression cycles with 100 mmHg static pressure applied over the mid-tibialis region of the right limb whereas the left uncompressed limb served as the intra-animal control...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29212904/dendritic-cell-ripk1-maintains-immune-homeostasis-by-preventing-inflammation-and-autoimmunity
#14
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...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29212215/betanodavirus-b2-protein-triggers-apoptosis-and-necroptosis-in-lung-cancer-cells-that-suppresses-autophagy
#15
Hsuan-Wen Chiu, Yu-Chin Su, Jiann-Ruey Hong
The betanodavirus B2 protein targets the mitochondria and acts as a "death factor", but its effect on lung cancer cells is unknown. We examined the effect of the B2 protein on triggering apoptosis or necroptosis via P53-dependent and P53-independent pathways and increased in suppression of autophagy. The B2 protein targets the mitochondria of A549 (P53+/+) and H1299 (P53-/-) lung cancer cells due to a specific signal sequence (41RTFVISAHAA50). This triggers generation of reactive oxygen species within the mitochondria, and a minor stress response in A549 cells, but a strong stress response in H1299 cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203926/pandemic-h1n1-influenza-a-viruses-suppress-immunogenic-ripk3-driven-dendritic-cell-death
#16
Boris M Hartmann, Randy A Albrecht, Elena Zaslavsky, German Nudelman, Hanna Pincas, Nada Marjanovic, Michael Schotsaert, Carles Martínez-Romero, Rafael Fenutria, Justin P Ingram, Irene Ramos, Ana Fernandez-Sesma, Siddharth Balachandran, Adolfo García-Sastre, Stuart C Sealfon
The risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host-pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29203883/abin-1-regulates-ripk1-activation-by-linking-met1-ubiquitylation-with-lys63-deubiquitylation-in-tnf-rsc
#17
Slawomir A Dziedzic, Zhenyi Su, Vica Jean Barrett, Ayaz Najafov, Adnan K Mookhtiar, Palak Amin, Heling Pan, Li Sun, Hong Zhu, Averil Ma, Derek W Abbott, Junying Yuan
Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1...
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29200200/wogonin-protects-against-cisplatin-induced-acute-kidney-injury-by-targeting-ripk1-mediated-necroptosis
#18
Xiao-Ming Meng, Hai-Di Li, Wei-Feng Wu, Patrick Ming-Kuen Tang, Gui-Ling Ren, Li Gao, Xiao-Feng Li, Yang Yang, Tao Xu, Tao-Tao Ma, Zeng Li, Cheng Huang, Lei Zhang, Xiong-Wen Lv, Jun Li
Acute kidney injury (AKI), characterized by aggressive inflammatory responses and destruction of renal resident cells, can cause abrupt kidney dysfunction. To date, effective therapy for AKI is lacking. In this study, we evaluated the renoprotective effect of wogonin, an herbal active compound, using a cisplatin-induced AKI mouse model. In vivo results show that wogonin substantially suppressed the increased levels of serum creatinine and blood urea nitrogen (BUN) almost to the normal level. Wogonin also attenuated tubular damage, shown by PAS staining, electron microscopy and molecular analysis of KIM-1...
December 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29175336/simultaneous-flow-cytometric-immunophenotyping-of-necroptosis-apoptosis-and-rip1-dependent-apoptosis
#19
H L Lee, R Pike, M H A Chong, A Vossenkamper, G Warnes
Flow cytometry was been widely used to measure apoptosis for many decades but the researcher has no definitive way of determining other forms of cell death using this technology. The use of Western Blot technology has numerous drawbacks in that all the cells in the sample whether live, dead or maybe undergoing multiple discrete forms of cell death are analysed as one population. Flow cytometry given that it can analyse different sub-populations of cells within a sample would reveal the expression of cell death markers within these sub-populations rather than just give a single result from the entire population...
November 23, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29171784/necroptosis-promotes-autophagy-dependent-upregulation-of-damp-and-results-in-immunosurveillance
#20
Sheng-Yen Lin, Sung-Yuan Hsieh, Yi-Ting Fan, Wen-Chi Wei, Pei-Wen Hsiao, Dai-Hua Tsai, Tzong-Shoon Wu, Ning-Sun Yang
Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity...
November 24, 2017: Autophagy
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