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https://www.readbyqxmd.com/read/28927431/role-of-the-sigma-1-receptor-chaperone-in-rod-and-cone-photoreceptor-degenerations-in-a-mouse-model-of-retinitis-pigmentosa
#1
Huan Yang, Yingmei Fu, Xinying Liu, Pawan K Shahi, Timur A Mavlyutov, Jun Li, Annie Yao, Steven Z-W Guo, Bikash R Pattnaik, Lian-Wang Guo
BACKGROUND: Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a potential retina-protective therapeutic target. In particular, pharmacological activation of S1R was recently shown to rescue cones in the rd10 mouse, a rod Pde6b mutant that recapitulates the RP pathology of autonomous rod degeneration followed by secondary death of cones. The mechanisms underlying the S1R protection for cones are not understood in detail...
September 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28923396/smac-mimetics-and-type-ii-interferon-synergistically-induce-necroptosis-in-various-cancer-cell-lines
#2
Michael John Cekay, Stefanie Roesler, Tanja Frank, Anne-Kathrin Knuth, Ines Eckhardt, Simone Fulda
Since cancer cells often evade apoptosis, induction of necroptosis as another mode of programmed cell death is considered as a promising therapeutic alternative. Here, we identify a novel synergistic interaction of Smac mimetics that antagonize x-linked Inhibitor of Apoptosis (XIAP), cellular Inhibitor of Apoptosis (cIAP) 1 and 2 with interferon (IFN)γ to induce necroptosis in apoptosis-resistant cancer cells in which caspase activation is blocked. The synergistic is confirmed by calculation of combination indices (CIs) and found in both solid and hematological cancer cell lines as well as for different Smac mimetics (i...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28887702/necroptosis-may-be-a-novel-mechanism-for-cardiomyocyte-death-in-acute-myocarditis
#3
Fei Zhou, Xuejun Jiang, Lin Teng, Jun Yang, Jiawang Ding, Chao He
In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28885615/necroptosis-in-microglia-contributes-to-neuroinflammation-and-retinal-degeneration-through-tlr4-activation
#4
Zijing Huang, Tian Zhou, Xiaowei Sun, Yingfeng Zheng, Bing Cheng, Mei Li, Xialin Liu, Chang He
Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice...
September 8, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28863321/the-role-of-necroptosis-in-status-epilepticus-induced-brain-injury-in-juvenile-rats
#5
Qianyun Cai, Jing Gan, Rong Luo, Yi Qu, Shiping Li, Chaomin Wan, Dezhi Mu
PURPOSE: To study the role of necroptosis in status epilepticus (SE)-induced injury in the developing brain and the possible associations of necroptosis with epileptogenesis and cognitive dysfunction. METHODS: The lithium-pilocarpine epilepsy model was reproduced in male rats at postnatal day 25. Propidium iodide (PI) staining was used to detect cell death after SE. Transmission electron microscopy (TEM) was performed to observe morphological changes in injured neurons...
August 29, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28845215/ppar-%C3%AE-activation-prevents-septic-cardiac-dysfunction-via-inhibition-of-apoptosis-and-necroptosis
#6
Shiyan Peng, Junmei Xu, Wei Ruan, Suobei Li, Feng Xiao
Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28844856/rip3-and-pmlkl-promote-necroptosis-induced-inflammation-and-alter-membrane-permeability-in-intestinal-epithelial-cells
#7
Anna Negroni, Eleonora Colantoni, Maria Pierdomenico, Francesca Palone, Manuela Costanzo, Salvatore Oliva, Antonio Tiberti, Salvatore Cucchiara, Laura Stronati
BACKGROUND: Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). AIMS: The aim of this study is to examine in depth in vitro and ex vivo the contribution of necroptosis to intestinal inflammation. METHODS: In vitro: we used an intestinal cell line, HCT116RIP3, produced in our laboratory and overexpressing RIP3. Ex vivo: intestinal mucosal biopsies were taken from patients with inflammatory bowel disease (IBD) (20 with Crohn's disease; 20 with ulcerative colitis) and from 20 controls...
August 10, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28816233/shikonin-induces-glioma-cell-necroptosis-in-vitro-by-ros-overproduction-and-promoting-rip1-rip3-necrosome-formation
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
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
#14
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...
October 1, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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