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https://www.readbyqxmd.com/read/28811972/uncovering-the-immunotherapeutic-cycle-initiated-by-p19arf-and-interferon-%C3%AE-gene-transfer-to-cancer-cells-an-inducer-of-immunogenic-cell-death
#1
REVIEW
Ruan F V Medrano, Aline Hunger, João P P Catani, Bryan E Strauss
Simultaneous reestablishment of p53/p19(Arf) and interferon-β pathways in melanoma cells culminates in a cell death process that displays features of necroptosis along with the release of immunogenic cell death molecules and unleashes an antitumor immune response mediated by natural killer cells, neutrophils as well as CD4(+) and CD8(+) T lymphocytes.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810529/silymarin-induces-a-multi-targeted-cell-death-process-in-the-human-colon-cancer-cell-line-ht-29
#2
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...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28807105/ripk1-ripk3-mlkl-dependent-necrosis-promotes-the-aging-of-mouse-male-reproductive-system
#3
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/28803066/a-novel-ripk1-inhibitor-that-prevents-retinal-degeneration-in-a-rat-glaucoma-model
#4
Yun-Ju Do, Jee-Won Sul, Ki-Hong Jang, Nam Sook Kang, Young-Hoon Kim, Young-Gwan Kim, Eunhee Kim
In glaucoma, retinal ganglion cells (RGCs) are exposed to ischemic stress with elevation of the intraocular pressure and are subsequently lost. Necroptosis, a type of regulated necrosis, is known to play a pivotal role in this loss. We observed that receptor-interacting protein kinase 1 (RIPK1), the key player of necroptosis, was activated by diverse ischemic stresses, including TCZ, chemical hypoxia (CH), and oxygen glucose deprivation (OGD). In this study, we introduce a RIPK1-inhibitory compound (RIC) with a novel scaffold...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28801344/frontline-science-macrophage-derived-exosomes-promote-neutrophil-necroptosis-following-hemorrhagic-shock
#5
Yang Jiao, Zhigang Li, Patricia A Loughran, Erica K Fan, Melanie J Scott, Yuehua Li, Timothy R Billiar, Mark A Wilson, Xueyin Shi, Jie Fan
Hemorrhagic shock (HS) renders patients susceptible to development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) through mechanisms that are, as yet, unclear. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. In this study, we investigated the mechanisms of alveolar macrophage (AMϕ) effects on PMN necroptosis following HS...
August 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28783694/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#6
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/28771230/hyperosmotic-stress-enhances-cytotoxicity-of-smac-mimetics
#7
Sebastian Bittner, Gertrud Knoll, Martin Ehrenschwender
Inhibitors of apoptosis (IAP) proteins contribute to cell death resistance in malignancies and emerged as promising targets in cancer therapy. Currently, small molecules mimicking the IAP-antagonizing activity of endogenous second mitochondria-derived activator of caspases (SMAC) are evaluated in phase 1/2 clinical trials. In cancer cells, SMAC mimetic (SM)-mediated IAP depletion induces tumor necrosis factor (TNF) secretion and simultaneously sensitizes for TNF-induced cell death. However, tumor cells lacking SM-induced autocrine TNF release survive and thus limit therapeutic efficacy...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28770700/detection-of-necroptosis-in-ligand-mediated-and-hypoxia-induced-injury-of-hepatocytes-using-a-novel-optic-probe-detecting-receptor-interacting-protein-rip-1-rip3-binding
#8
Sanae Haga, Akira Kanno, Takeaki Ozawa, Naoki Morita, Mami Asano, Michitaka Ozaki
Liver injury is often observed in various pathological conditions including posthepatectomy state and cancer chemotherapy. It occurs mainly as a consequence of the combined necrotic and apoptotic types of cell death. In order to study liver/hepatocyte injury by necrotic type of cell death, we studied signal-regulated necrosis (necroptosis) by newly developing an optic probe detecting receptor-interacting protein (RIP)1/RIP3 binding, an essential process for necroptosis induction. In the mouse hepatocyte cell line, TIB-73 cells, TNF-a/cycloheximide (T/C) induced RIP1/3 binding only when caspase activity was suppressed by z-VAD-fmk (zVAD), a caspase-specific inhibitor...
July 21, 2017: Oncology Research
https://www.readbyqxmd.com/read/28767448/selective-cytotoxicity-of-vanadium-complexes-on-human-pancreatic-ductal-adenocarcinoma-cell-line-by-inducing-necroptosis-apoptosis-and-mitotic-catastrophe-process
#9
Szymon Kowalski, Stanisław Hać, Dariusz Wyrzykowski, Agata Zauszkiewicz-Pawlak, Iwona Inkielewicz-Stępniak
The pancreatic cancer is the fourth leading cause of cancer-related death and characterized by one of the lowest five-year survival rate. The current therapeutic options are demonstrating minimal effectiveness, therefore studies on new potential anticancer compounds, with non-significant side effects are highly desirable. Recently, it was demonstrated that vanadium compounds, in particular organic derivatives, exhibit anticancer properties against different type of tumor as well as favorable biodistribution from a pancreatic cancer treatment perspective...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765050/role-of-ubiquitination-and-proteolysis-in-the-regulation-of-pro-and-anti-apoptotic-tnf-r1-signaling
#10
Jürgen Fritsch, Philipp Zingler, Vinzenz Särchen, Anna Laura Heck, Stefan Schütze
Tumor Necrosis Factor Receptor 1 (TNF-R1) transmits various intracellular signaling cascades leading to diverse biological outcomes, ranging from proliferation, differentiation, survival to the induction of various forms of cell death (i.e. apoptosis, necrosis, necroptosis). These signaling pathways have to be tightly regulated. Proteolysis is an important regulatory mechanism in TNF-R1 pro-apoptotic as well as anti-apoptotic/pro-inflammatory signaling. Some key players in these signaling cascades are known (mainly the caspase-family of proteases and a previously unrecognized "lysosomal death pathway" involving cathepsins), however the interaction of proteases in the regulation of TNF signaling is still enigmatic...
July 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in-pancreatic-carcinoma
#11
Yangchun Xie, Shan Zhu, Meizuo Zhong, Minghua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of non-apoptotic 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
https://www.readbyqxmd.com/read/28763140/necroptosis-in-the-periodontal-homeostasis-signals-emanating-from-dying-cells
#12
REVIEW
Jiao Li, XiaoJing Ke, Fuhua Yan, Lang Lei, Houxuan Li
Periodontal tissues are constantly exposed to microbial stimuli. The equilibrium between microbes and host defense system helps maintain the homeostasis in the periodontal microenvironment. Growth of pathogenic bacteria in dental biofilms may induce proinflammatory cytokine production to recruit sentinel cells, mainly neutrophils and monocytes into the gingival sulcus or the periodontal pocket. Moreover,dybiosis with over-growth of anaerobic pathogens, such as Porphyromonas gingivalis and Tannerella forsythia, may induce death of both immune cells and host resident cells...
August 1, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28759952/expression-and-genetic-polymorphism-of-necroptosis-related-protein-ripk1-is-correlated-with-severe-hepatic-ischemia-reperfusion-injury-and-prognosis-after-hepatectomy-in-hepatocellular-carcinoma-patients
#13
Chen Yao, Gang Li, Ming Cai, Yeyong Qian, Liqin Wang, Li Xiao, Friedrich Thaiss, Bingyi Shi
OBJECTIVES: The goal of our study was to assess the prognostic impact of the necroptosis relative protein RIPK1 genetic polymorphism in ischemia-reperfusion injury and survival after hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: In this study, expression of RIPK1 and its genetic polymorphism(rs2272990) were examined in plasma of 44 HCC patients. All these patients were undergoing partial hepatectomy. The prognostic values of RIPK1 genetic polymorphism for tumor development and survival, and ischemia-reperfusion injury after hepatectomy were further determined...
July 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28758999/necroptosis-activation-in-alzheimer-s-disease
#14
Antonella Caccamo, Caterina Branca, Ignazio S Piras, Eric Ferreira, Matthew J Huentelman, Winnie S Liang, Ben Readhead, Joel T Dudley, Elizabeth E Spangenberg, Kim N Green, Ramona Belfiore, Wendy Winslow, Salvatore Oddo
Alzheimer's disease (AD) is characterized by severe neuronal loss; however, the mechanisms by which neurons die remain elusive. Necroptosis, a programmed form of necrosis, is executed by the mixed lineage kinase domain-like (MLKL) protein, which is triggered by receptor-interactive protein kinases (RIPK) 1 and 3. We found that necroptosis was activated in postmortem human AD brains, positively correlated with Braak stage, and inversely correlated with brain weight and cognitive scores. In addition, we found that the set of genes regulated by RIPK1 overlapped significantly with multiple independent AD transcriptomic signatures, indicating that RIPK1 activity could explain a substantial portion of transcriptomic changes in AD...
July 24, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28752362/necrostatin-1-protects-against-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-by-preventing-tlr4-and-rage-signaling
#15
Seok-Joo Kim, Sun-Mee Lee
Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome results in massive inflammation and hepatocyte death. Necroptosis is a regulated form of necrotic cell death that is emerging as a crucial control point for inflammatory diseases. The kinases receptor interacting protein (RIP) 1 and RIP3 are known as key modulators of necroptosis. In this study, we investigated the impact of necroptosis in the pathogenesis of FHF and molecular mechanisms, particularly its linkage to damage-associated molecular pattern (DAMP)-mediated pattern recognition receptor (PRR) signaling pathways...
July 27, 2017: Inflammation
https://www.readbyqxmd.com/read/28744127/necrostatin-1-attenuates-early-brain-injury-after-subarachnoid-hemorrhage-in-rats-by-inhibiting-necroptosis
#16
Fuxiang Chen, Xingfen Su, Zhangya Lin, Yuanxiang Lin, Lianghong Yu, Jiawei Cai, Dezhi Kang, Liwen Hu
Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH (P<0...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28732308/ripk3-induces-mitochondrial-apoptosis-via-inhibition-of-fundc1-mitophagy-in-cardiac-ir-injury
#17
Hao Zhou, Pingjun Zhu, Jun Guo, Nan Hu, Shuyi Wang, Dandan Li, Shunying Hu, Jun Ren, Feng Cao, Yundai Chen
Ripk3-required necroptosis and mitochondria-mediated apoptosis are the predominant types of cell death that largely account for the development of cardiac ischemia reperfusion injury (IRI). Here, we explored the effect of Ripk3 on mitochondrial apoptosis. Compared with wild-type mice, the infarcted area in Ripk3-deficient (Ripk3(-/-)) mice had a relatively low abundance of apoptotic cells. Moreover, the loss of Ripk3 protected the mitochondria against IRI and inhibited caspase9 apoptotic pathways. These protective effects of Ripk3 deficiency were relied on mitophagy activation...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28724891/hypoxia-inducible-factor-1-alpha-is-involved-in-rip-induced-necroptosis-caused-by-in-vitro-and-in-vivo-ischemic-brain-injury
#18
Xiao-Sa Yang, Tai-Long Yi, Sai Zhang, Zhong-Wei Xu, Ze-Qi Yu, Hong-Tao Sun, Cheng Yang, Yue Tu, Shi-Xiang Cheng
Necroptosis, a novel type of programmed cell death, is involved in stroke-induced ischemic brain injury. Although studies have sought to explore the mechanisms of necroptosis, its signaling pathway has not yet to be completely elucidated. Thus, we used oxygen-glucose deprivation (OGD) and middle cerebral artery occlusion (MCAO) models mimicking ischemic stroke (IS) conditions to investigate mechanisms of necroptosis. We found that OGD and MCAO induced cell death, local brain ischemia and neurological deficit, while zVAD-fmk (zVAD, an apoptotic inhibitor), GSK'872 (a receptor interacting protein kinase-3 (RIP3) inhibitor), and combined treatment alleviated cell death and ischemic brain injury...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723681/inhibition-of-necroptosis-attenuates-kidney-inflammation-and-interstitial-fibrosis-induced-by-unilateral-ureteral-obstruction
#19
Xia Xiao, Chunyang Du, Zhe Yan, Yonghong Shi, Huijun Duan, Yunzhuo Ren
BACKGROUND: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury...
July 20, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28723543/necroptosis-last-message-in-a-bubble
#20
Peter Vandenabeele, Franck Riquet, Benjamin Cappe
RIPK3 kinase-mediated phosphorylation of MLKL pseudokinase is the execution event of necroptosis. Two independent reports-in Immunity (Yoon et al., 2017) and Cell (Gong et al., 2017)-reveal that MLKL affects homeostatic membrane trafficking and necroptosis-enhanced bubble formation involving interaction with the ESCRT machinery.
July 18, 2017: Immunity
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