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https://www.readbyqxmd.com/read/28816233/shikonin-induces-glioma-cell-necroptosis-in-vitro-by-ros-overproduction-and-promoting-rip1-rip3-necrosome-formation
#1
Bin Lu, Xu Gong, Zong-Qi Wang, Ye Ding, Chen Wang, Tian-Fei Luo, Mei-Hua Piao, Fan-Kai Meng, Guang-Fan Chi, Yi-Nan Luo, Peng-Fei Ge
Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in regulation of necroptosis remains elusive. In this study, we investigated how shikonin, a necroptosis inducer for cancer cells, regulated the signaling leading to necroptosis in glinoma cells in vitro. Treatment with shikonin (2-10 μmol/L) dose-dependently triggered necrosis and induced overproduction of intracellular ROS in rat C6 and human SHG-44, U87 and U251 glioma cell lines...
August 17, 2017: Acta Pharmacologica Sinica
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
#2
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/28752362/necrostatin-1-protects-against-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-by-preventing-tlr4-and-rage-signaling
#3
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
#4
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/28724891/hypoxia-inducible-factor-1-alpha-is-involved-in-rip-induced-necroptosis-caused-by-in-vitro-and-in-vivo-ischemic-brain-injury
#5
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
#6
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/28716527/identification-of-a-synergistic-combination-of-smac-mimetic-and-bortezomib-to-trigger-cell-death-in-b-cell-non-hodgkin-lymphoma-cells
#7
Irfan Ahmed Bhatti, Behnaz Ahangarian Abhari, Simone Fulda
Recently, copy number gains and increased expression levels of cIAP1 and cIAP2 have been reported in B-cell non-Hodgkin lymphomas (NHL). Therefore, we investigated the therapeutic potential of the Smac mimetic BV6 that antagonizes cIAP1/2 and XIAP. Here, we discover that subtoxic concentrations of BV6 prime B-cell NHL cells to proteasome inhibitor Bortezomib-induced cell death. Synergistic induction of cell death by BV6 and Bortezomib is confirmed by calculation of combination index in different cell lines, emphasizing the broader relevance of this combination...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28709622/genipin-protects-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-through-suppression-of-the-necroptosis-mediated-inflammasome-signaling
#8
Min-Jong Seo, Jeong-Min Hong, Seok-Joo Kim, Sun-Mee Lee
Acute liver failure (ALF) is a life-threatening syndrome resulting from massive inflammation and hepatocyte death. Necroptosis, a programmed cell death controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, has been shown to play an important role in regulating inflammation via crosstalk between other intracellular signaling. The inflammasome is a major intracellular multiprotein that induces inflammatory responses by mediating immune cell infiltration, thus potentiating injury. Genipin, a major active compound of the gardenia fruit, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties...
July 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28703808/rip3-attenuates-the-pancreatic-damage-induced-by-deletion-of-atg7
#9
Xiaodong Zhou, Li Xie, Leizhou Xia, Frank Bergmann, Markus W Büchler, Guido Kroemer, Thilo Hackert, Franco Fortunato
Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28661482/necroptosis-in-neurodegenerative-diseases-a-potential-therapeutic-target
#10
REVIEW
Shuo Zhang, Mi-Bo Tang, Hai-Yang Luo, Chang-He Shi, Yu-Ming Xu
Neurodegenerative diseases are a group of chronic progressive disorders characterized by neuronal loss. Necroptosis, a recently discovered form of programmed cell death, is a cell death mechanism that has necrosis-like morphological characteristics. Necroptosis activation relies on the receptor-interacting protein (RIP) homology interaction motif (RHIM). A variety of RHIM-containing proteins transduce necroptotic signals from the cell trigger to the cell death mediators RIP3 and mixed lineage kinase domain-like protein (MLKL)...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28660207/chlamydia-muridarum-infection-of-macrophages-stimulates-il-1%C3%AE-secretion-and-cell-death-via-activation-of-caspase-1-in-an-rip3-independent-manner
#11
Lixiang Chen, Xue Liu, Xin Yu, Rongrong Ren, Chao Wang, Rui Zhao, Guangxun Meng, Shun Li, Xiaohui Zhou
Chlamydiae are Gram-negative bacteria, which replicate exclusively in the infected host cells. Infection of the host cells by Chlamydiae stimulates the innate immune system leading to an inflammatory response, which is manifested not only by secretion of proinflammatory cytokines such as IL-1β from monocytes, macrophages, and dendritic cells, but also possibly by cell death mediated by Caspase-1 pyroptosis. RIP3 is a molecular switch that determines the development of necrosis or inflammation. However, the involvement of RIP3 in inflammasome activation by Chlamydia muridarum infection has not been clarified...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28651499/necroptosis-in-cancer-an-angel-or-a-demon
#12
REVIEW
Tianzhen Wang, Yinji Jin, Weiwei Yang, Lei Zhang, Xiaoming Jin, Xi Liu, Yan He, Xiaobo Li
In the past few decades, apoptosis has been regarded as the only form of programmed cell death. However, the traditional view has been challenged by the identification of several forms of regulated necrosis, including necroptosis. Necroptosis is typified by a necrotic cell death morphology and is controlled by RIP1, RIP3, and mixed lineage kinase domain-like protein. The physiological role of necroptosis is to serve as a "fail-safe" form of cell death for cells that fail to undergo apoptosis during embryonic development and disease defense...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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
#13
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/28647341/suppression-of-autophagic-flux-contributes-to-cardiomyocyte-death-by-activation-of-necroptotic-pathways
#14
Makoto Ogasawara, Toshiyuki Yano, Masaya Tanno, Koki Abe, Satoko Ishikawa, Takayuki Miki, Atsushi Kuno, Toshiyuki Tobisawa, Shingo Muratsubaki, Kouhei Ohno, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Tetsuji Miura
BACKGROUND: The role of necroptosis in myocardial injury has not been fully characterized. Here we examined roles of mitochondrial permeability transition pore (mPTP) and autophagy in necroptosis of cardiomyocytes. METHODS AND RESULTS: In H9c2 cells, necroptosis was induced by treatment with TNF-α (TNF) and z-VAD-fmk (zVAD) for 24h, and necroptotic death was determined by LDH release (as % of total). TNF/zVAD increased LDH release from 16.6±4.3% to 60.6±2.7%, and the LDH release was suppressed by necrostatin-1 (29...
June 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28626232/the-rip3-rip1-nf-%C3%AE%C2%BAb-signaling-axis-is-dispensable-for-necroptotic-cells-to-elicit-cross-priming-of-cd8-t-cells
#15
Junming Ren, Xian Jia, Yihao Zhao, Wenke Shi, Jiongcong Lu, Yingying Zhang, Jianfeng Wu, Bo Liang, Rui Wu, Guo Fu, Jiahuai Han
No abstract text is available yet for this article.
July 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28592284/biogenic-selenium-nanoparticles-induce-ros-mediated-necroptosis-in-pc-3-cancer-cells-through-tnf-activation
#16
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/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#17
Keren Zhou, Ligen Shi, Zhen Wang, Jingyi Zhou, Anatol Manaenko, Cesar Reis, Sheng Chen, Jianmin Zhang
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection...
September 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28574501/rip1-kinase-activity-dependent-roles-in-embryonic-development-of-fadd-deficient-mice
#18
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...
August 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28572508/cardioprotective-role-of-traf2-by-suppressing-apoptosis-and-necroptosis
#19
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/28564603/2-hg-inhibits-necroptosis-by-stimulating-dnmt1-dependent-hypermethylation-of-the-rip3-promoter
#20
Zhentao Yang, Bin Jiang, Yan Wang, Hengxiao Ni, Jia Zhang, Jinmei Xia, Minggang Shi, Li-Man Hung, Jingsong Ruan, Tak Wah Mak, Qinxi Li, Jiahuai Han
2-hydroxyglutarate-(2-HG)-mediated inhibition of TET2 activity influences DNA hypermethylation in cells harboring mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2). Here, we show that 2-HG also regulates DNA methylation mediated by DNA methyltransferase 1 (DNMT1). DNMT1-dependent hypermethylation of the RIP3 promoter occurred in both IDH1 R132Q knockin mutant mouse embryonic fibroblast (MEFs) and 2-HG-treated wild-type (WT) MEFs. We found that 2-HG bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis...
May 30, 2017: Cell Reports
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