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https://www.readbyqxmd.com/read/29772481/vascular-peroxide-1-promotes-ox-ldl-induced-programmed-necrosis-in-endothelial-cells-through-a-mechanism-involving-%C3%AE-catenin-signaling
#1
Yin-Zhuang Zhang, Lei Wang, Jie-Jie Zhang, Xiao-Ming Xiong, Di Zhang, Xuan-Meng Tang, Xiu-Ju Luo, Qi-Lin Ma, Jun Peng
BACKGROUND AND AIMS: Vascular peroxidase 1 (VPO1) plays a key role in mediation of cardiovascular oxidative injury. This study aims to determine whether VPO1 can promote programmed necrosis of endothelial cells and the underlying mechanisms. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 48 h to induce cell injury, which showed an elevation in cell necrosis (reflected by the increased propidium iodide (PI) positive-staining cells, LDH release and decreased cell viability), concomitant with an increase in programmed necrosis-relevant proteins including receptor-interacting protein kinase 1/3 (RIPK1/3), p-RIPK3 and mixed lineage kinase domain like (MLKL); these phenomena were attenuated by necrostatin-1(Nec-1) and RIPK3 siRNA...
May 3, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29770189/hydrogen-inhalation-improves-mouse-neurological-outcomes-after-cerebral-ischemia-reperfusion-independent-of-anti-necroptosis
#2
Jun-Long Huang, Wen-Wu Liu, Xue-Jun Sun
This study aimed to investigate the role of necroptosis in the neuroprotection of hydrogen in a mouse model of cerebral ischemia/reperfusion (I/R) injury. C57BL mice were randomly divided into sham group, I/R group, hydrogen/oxygen group (HO), nitrogen/oxygen group (NO). Middle cerebral artery occlusion (MCAO) for 1 hour followed by reperfusion was introduced to animals which were allowed to inhale 66.7% hydrogen/33.3% oxygen for 90 minutes since the beginning of reperfusion. Mice in NO group inhaled 66.7% nitrogen/33...
January 2018: Medical Gas Research
https://www.readbyqxmd.com/read/29760953/hyperglycemia-potentiates-a-shift-from-apoptosis-to-rip1-dependent-necroptosis
#3
William D McCaig, Payal S Patel, Sergey A Sosunov, Nicole L Shakerley, Tori A Smiraglia, Miranda M Craft, Katharine M Walker, Matthew A Deragon, Vadim S Ten, Timothy J LaRocca
Apoptosis and necroptosis are the primary modes of eukaryotic cell death, with apoptosis being non-inflammatory while necroptosis is highly inflammatory. We previously demonstrated that, once activated, necroptosis is enhanced by hyperglycemia in several cell types. Here, we determine if hyperglycemia affects apoptosis similarly. We show that hyperglycemia does not enhance extrinsic apoptosis but potentiates a shift to RIP1-dependent necroptosis. This is due to increased levels and activity of RIP1, RIP3, and MLKL, as well as decreased levels and activity of executioner caspases under hyperglycemic conditions following stimulation of apoptosis...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29746630/ripk3-mlkl-mediated-neuronal-necroptosis-modulates-the-m1-m2-polarization-of-microglia-macrophages-in-the-ischemic-cortex
#4
Jiping Yang, Youyi Zhao, Li Zhang, Hong Fan, Chuchu Qi, Kun Zhang, Xinyu Liu, Lin Fei, Siwei Chen, Mengmeng Wang, Fang Kuang, Yazhou Wang, Shengxi Wu
Cell death and subsequent inflammation are 2 key pathological changes occurring in cerebral ischemia. Active microglia/macrophages play a double-edged role depending on the balance of their M1/M2 phenotypes. Necrosis is the predominant type of cell death following ischemia. However, how necrotic cells modulate the M1/M2 polarization of microglia/macrophages remains poorly investigated. Here, we reported that ischemia induces a rapid RIPK3/MLKL-mediated neuron-dominated necroptosis, a type of programmed necrosis...
May 9, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29729104/the-impact-of-diet-induced-hepatic-steatosis-in-a-murine-model-of-hepatic-ischemia-reperfusion-injury
#5
Kim H H Liss, Kyle S McCommis, Kari T Chambers, Terri A Pietka, George G Schweitzer, Sara L Park, ILKe Nalbantoglu, Carla J Weinheimer, Angela M Hall, Brian N Finck
The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade and end stage liver disease secondary to nonalcoholic steatohepatitis has become one of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. While in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia reperfusion injury and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers...
May 5, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29725301/necrostatin-1-attenuates-cisplatin-induced-nephrotoxicity-through-suppression-of-apoptosis-and-oxidative-stress-and-retains-klotho-expression
#6
Yichun Ning, Yiqin Shi, Jing Chen, Nana Song, Jieru Cai, Yi Fang, Xiaofang Yu, Jun Ji, Xiaoqiang Ding
Aim: Cisplatin is an effective chemotherapeutic drug, but the application in clinical is greatly limited by its nephrotoxicity. Necrostatin-1 (Nec-1), an inhibitor of RIP1 kinase, has been reported to inhibit RIP-mediated necroptosis. The aim of this study is to detect the protective effects of Nec-1 on the nephrotoxicity of cisplatin and to investigate its renoprotection mechanism. Methods: 8-week-old male C57BL/6 mice were randomly assigned into four groups: Control, Nec-1, Cisplatin, and Cisplatin+Nec-1...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29720570/ripk3-mediates-pathogenesis-of-experimental-ventilator-induced-lung-injury
#7
Ilias I Siempos, Kevin C Ma, Mitsuru Imamura, Rebecca M Baron, Laura E Fredenburgh, Jin-Won Huh, Jong-Seok Moon, Eli J Finkelsztein, Daniel S Jones, Michael Torres Lizardi, Edward J Schenck, Stefan W Ryter, Kiichi Nakahira, Augustine Mk Choi
In patients requiring ventilator support, mechanical ventilation (MV) may induce acute lung injury (ventilator-induced lung injury [VILI]). VILI is associated with substantial morbidity and mortality in mechanically ventilated patients with and without acute respiratory distress syndrome. At the cellular level, VILI induces necrotic cell death. However, the contribution of necroptosis, a programmed form of necrotic cell death regulated by receptor-interacting protein-3 kinase (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), to the development of VILI remains unexplored...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29703889/necroptosis-promotes-cell-autonomous-activation-of-proinflammatory-cytokine-gene-expression
#8
Kezhou Zhu, Wei Liang, Zaijun Ma, Daichao Xu, Shuangyi Cao, Xiaojuan Lu, Nan Liu, Bing Shan, Lihui Qian, Junying Yuan
Necroptosis, a form of regulated necrotic cell death, is mediated by receptor interacting protein 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). However, the mechanism by which necroptosis promotes inflammation is still unclear. Here we report that the expression of cytokines is robustly upregulated in a cell-autonomous manner during necroptosis induced by tumor necrosis factor alpha (TNFα). We demonstrate that TNFα-induced necroptosis leads to two waves of cytokine production. The first wave, more transient and weaker than the second, is in response to TNFα alone; whereas the second wave depends upon the necroptotic signaling...
April 27, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29696779/necroptosis-increases-with-age-and-is-reduced-by-dietary-restriction
#9
Sathyaseelan S Deepa, Archana Unnikrishnan, Stephanie Matyi, Niran Hadad, Arlan Richardson
Necroptosis is a newly identified programmed cell death pathway that is highly proinflammatory due to the release of cellular components that promote inflammation. To determine whether necroptosis might play a role in inflammaging, we studied the effect of age and dietary restriction (DR) on necroptosis in the epididymal white adipose tissue (eWAT), a major source of proinflammatory cytokines. Phosphorylated MLKL and RIPK3, markers of necroptosis, were increased 2.7- and 1.9-fold, respectively, in eWAT of old mice compared to adult mice, and DR reduced P-MLKL and P-RIPK3 to levels similar to adult mice...
April 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29695863/lubac-is-essential-for-embryogenesis-by-preventing-cell-death-and-enabling-haematopoiesis
#10
Nieves Peltzer, Maurice Darding, Antonella Montinaro, Peter Draber, Helena Draberova, Sebastian Kupka, Eva Rieser, Amanda Fisher, Ciaran Hutchinson, Lucia Taraborrelli, Torsten Hartwig, Elodie Lafont, Tobias L Haas, Yutaka Shimizu, Charlotta Böiers, Aida Sarr, James Rickard, Silvia Alvarez-Diaz, Michael T Ashworth, Allison Beal, Tariq Enver, John Bertin, William Kaiser, Andreas Strasser, John Silke, Philippe Bouillet, Henning Walczak
The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death2-8 . In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype9-11 ...
May 2018: Nature
https://www.readbyqxmd.com/read/29686269/lysosomal-damage-after-spinal-cord-injury-causes-accumulation-of-ripk1-and-ripk3-proteins-and-potentiation-of-necroptosis
#11
Shuo Liu, Yun Li, Harry M C Choi, Chinmoy Sarkar, Eugene Y Koh, Junfang Wu, Marta M Lipinski
Necroptosis, a regulated necrosis pathway mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), is induced following spinal cord injury (SCI) and thought to contribute to neuronal and glial cell death. However, mechanisms leading to activation of necroptosis after SCI remain unclear. We have previously shown that autophagy, a catabolic pathway facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner, is inhibited following SCI in rats. Our current data confirm that inhibition of autophagy also occurs after thoracic contusive SCI in the mouse model, as indicated by accumulation of both the autophagosome marker, LC3-II and autophagy cargo protein, p62/SQSTM1...
April 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29678581/molecular-and-histological-study-on-the-effects-of-non-thermal-irreversible-electroporation-on-the-liver
#12
Yanfang Zhang, Chenang Lyu, Yu Liu, Yanpeng Lv, Tammy T Chang, Boris Rubinsky
Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon in which certain electric fields delivered across the cell membrane in tissue, cause cell death, without affecting the extracellular matrix. "Minimally invasive regenerative surgery" is a new medical modality for treatment of end-stage organ or tissue failure in which exogenous cells are implanted in a decellularized niche in tissue, formed by the delivery of NTIRE electric fields across a targeted volume of tissue. We anticipate that the success of the procedure will depend on the time of implantation relative to the application of NTIRE...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29664014/rip-kinase-1-dependent-endothelial-necroptosis-underlies-systemic-inflammatory-response-syndrome
#13
Matija Zelic, Justine E Roderick, Joanne A O'Donnell, Jesse Lehman, Sung Eun Lim, Harish P Janardhan, Chinmay M Trivedi, Manolis Pasparakis, Michelle A Kelliher
Receptor interacting protein kinase 1 (RIPK1) has important kinase-dependent and kinase-independent scaffolding functions that activate or prevent apoptosis or necroptosis in a cell context-dependent manner. The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF-induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory "cytokine storm" has long been viewed as detrimental. Here, we demonstrate that cytokine and chemokine levels did not predict survival and, importantly, that kinase-inactive Ripk1D138N/D138N hematopoietic cells afforded little protection from TNF- or TNF/zVAD-induced shock in reconstituted mice...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29656768/a-rare-variant-in-mlkl-confers-susceptibility-to-apoe-%C3%A9-4-negative-alzheimer-s-disease-in-hong-kong-chinese-population
#14
Binbin Wang, Suying Bao, Zhigang Zhang, Xueya Zhou, Jing Wang, Yanhui Fan, Yan Zhang, Yan Li, Luhua Chen, Yizhen Jia, Jiang Li, Miaoxin Li, Wenhua Zheng, Nan Mu, Liqiu Wang, Zhe Yu, Dana S M Wong, Yalun Zhang, Joseph Kwan, Henry Ka-Fung Mak, Amirthagowri Ambalavanan, Sirui Zhou, Wangwei Cai, Jin Zheng, Shishu Huang, Guy A Rouleau, Wanling Yang, Ekaterina Rogaeva, Xu Ma, Peter St George-Hyslop, Leung Wing Chu, You-Qiang Song
Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than apolipoprotein E ɛ4 allele (ApoE ɛ4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kong Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls. Among the genes involved in immune function, we identified a rare stop-gain variant (p...
March 10, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29643440/bacterial-pore-forming-toxins-promote-the-activation-of-caspases-in-parallel-to-necroptosis-to-enhance-alarmin-release-and-inflammation-during-pneumonia
#15
Norberto Gonzalez-Juarbe, Kelley M Bradley, Ashleigh N Riegler, Luis F Reyes, Terry Brissac, Sang-Sang Park, Marcos I Restrepo, Carlos J Orihuela
Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29621771/low-necroptosis-process-predicts-poor-treatment-outcome-of-human-papillomavirus-positive-cervical-cancers-by-decreasing-tumor-associated-macrophages-m1-polarization
#16
Lin Li, Song Yu, Chunyi Zang
BACKGROUND/AIM: The aim of this study was to assess the functions of the necroptosis process on the prognosis of high-risk human papillomavirus (HR-HPV)-related cervical cancer. METHODS: PCR and western blotting were used to demonstrate the expression of the necroptosis marker, mixed lineage kinase domain-like protein (MLKL), in whole blood and peripheral blood mononuclears (PBMCs) of 89 cervical cancer patients and 15 healthy volunteers. Necroptosis levels and M1 polarization were determined in tumor co-cultured macrophages...
April 5, 2018: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/29621753/necroptosis-contributes-to-urban-particulate-matter-induced-airway-epithelial-injury
#17
Feng Xu, Man Luo, Lulu He, Yuan Cao, Wen Li, Songmin Ying, Zhihua Chen, Huahao Shen
BACKGROUND/AIMS: Necroptosis, a form of programmed necrosis, is involved in the pathologic process of several kinds of pulmonary diseases. However, the role of necroptosis in particulate matter (PM)-induced pulmonary injury remains unclear. The objective of this study is to investigate the involvement of necroptosis in the pathogenesis of PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction, both in vitro and in vivo. METHODS: PM was administered into human bronchial epithelial (HBE) cells or mouse airways, and the inflammatory response and mucus production were assessed...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29614353/necrosulfonamide-attenuates-the-spinal-cord-injury-via-necroptosis-inhibition
#18
Yongxiang Wang, Jingcheng Wang, Hua Wang, Xinmin Feng, Yuping Tao, Jiandong Yang, Jun Cai
Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. To investigate the effects of Necrosulfonamide (NSA) in the treatment of SCI, pathological condition, necroptosis related factors, mitochondrial function and ethological performance were detected. Pathological detection using HE staining was performed first. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA. No obvious toxicity on rat liver, kidney, heart and spleen was detected using HE staining...
March 31, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29606984/elevated-serum-levels-of-mixed-lineage-kinase-domain-like-protein-predict-survival-of-patients-during-intensive-care-unit-treatment
#19
Mihael Vucur, Christoph Roderburg, Lukas Kaiser, Anne Theres Schneider, Sanchari Roy, Sven Heiko Loosen, Mark Luedde, Christian Trautwein, Alexander Koch, Frank Tacke, Tom Luedde
Mixed lineage kinase domain-like (MLKL), a crucial regulator of necroptotic cell death, was shown to play a role in inflammatory diseases. However, its role as a biomarker in critical illness and sepsis is currently unknown. We analyzed serum levels of MLKL in 136 critically ill patients at admission to the intensive care unit (ICU) and after three days of ICU treatment. Results were compared with 36 healthy controls and correlated with clinical and laboratory patients' data. MLKL serum levels of critically ill patients at admission to the ICU were similar compared to healthy controls...
2018: Disease Markers
https://www.readbyqxmd.com/read/29598451/novel-drug-discovery-strategies-for-atherosclerosis-that-target-necrosis-and-necroptosis
#20
Isabelle Coornaert, Sam Hofmans, Lars Devisscher, Koen Augustyns, Pieter Van Der Veken, Guido R Y De Meyer, Wim Martinet
Formation and enlargement of a necrotic core play a pivotal role in atherogenesis. Since the discovery of necroptosis, which is a regulated form of necrosis, prevention of necrotic cell death has become an attractive therapeutic goal to reduce plaque formation. Areas covered: This review highlights the triggers and consequences of (unregulated) necrosis and necroptosis in atherosclerosis. The authors discuss different pharmacological strategies to inhibit necrotic cell death in advanced atherosclerotic plaques...
March 29, 2018: Expert Opinion on Drug Discovery
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