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https://www.readbyqxmd.com/read/28940129/the-role-of-smurf1-in-neuronal-necroptosis-after-lipopolysaccharide-induced-neuroinflammation
#1
Lifei Shao, Xiaojuan Liu, Shunxing Zhu, Chun Liu, Yilu Gao, Xide Xu
The role of inflammation in neurological disorders such as Alzheimer's disease and Parkinson's disease is gradually recognized and leads to an urgent challenge. Smad ubiquitination regulatory factor 1 (Smurf1), one member of the HECT family, is up-regulated by proinflammatory cytokines and associated with apoptosis in acute spinal cord injury. However, the function of Smurf1 through promoting neuronal necroptosis is still limited in the central nervous system (CNS). Hence, we developed a neuroinflammatory model in adult rats following lipopolysaccharide (LPS) lateral ventral injection to elaborate whether Smurf1 is involved in necroptosis in CNS injury...
September 22, 2017: Cellular and Molecular Neurobiology
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
#2
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
#3
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 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28900035/prion-protein-is-required-for-tumor-necrosis-factor-alpha-tnf%C3%AE-triggered-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-signaling-and-cytokine-production
#4
Gui-Ru Wu, Tian-Chen Mu, Zhen-Xing Gao, Jun Wang, Man-Sun Sy, Chao-yang Li
The expression of normal cellular prion protein (PrP) is required for the pathogenesis of prion diseases. However, the physiological functions of PrP remain ambiguous. Here, we identified PrP as being critical for tumor necrosis factor (TNF)α-triggered signaling in a human melanoma cell line, M2, and a pancreatic ductal cell adenocarcinoma cell line, BxPC-3. In M2 cells, TNFα upregulates the expression of p-I-kappa-B-kinase α/β (p-IKKα/β), p-p65, and p-JNK, but downregulates the IκBα protein, all of which are downstream signaling intermediates in the TNF receptor signaling cascade...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28892675/alkynyl-gold-i-complex-triggers-necroptosis-via-ros-generation-in-colorectal-carcinoma-cells
#5
Inés Mármol, María Virumbrales-Muñoz, Javier Quero, Cristina Sánchez-de-Diego, Luis Fernández, Ignacio Ochoa, Elena Cerrada, Mª Jesús Rodríguez Yoldi
Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC5H4)(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line...
August 31, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28887702/necroptosis-may-be-a-novel-mechanism-for-cardiomyocyte-death-in-acute-myocarditis
#6
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
#7
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/28871172/the-cytoplasmic-nuclear-receptor-rar%C3%AE-controls-rip1-initiated-cell-death-when-ciap-activity-is-inhibited
#8
Qing Xu, Siriporn Jitkaew, Swati Choksi, Chamila Kadigamuwa, Jianhui Qu, Moran Choe, Jonathan Jang, Chengyu Liu, Zheng-Gang Liu
Tumor necrosis factor (TNF) has a critical role in diverse cellular events including inflammation, apoptosis and necroptosis through different signaling complexes. However, little is known about how the transition from inflammatory signaling to the engagement of death pathways is modulated. Here we report that the cytoplasmic retinoic acid receptor gamma (RARγ) controls receptor-interacting protein kinase 1 (RIP1)-initiated cell death when cellular inhibitor of apoptosis (cIAP) activity is blocked. Through screening a short hairpin RNA library, we found that RARγ was essential for TNF-induced RIP1-initiated apoptosis and necroptosis...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28845215/ppar-%C3%AE-activation-prevents-septic-cardiac-dysfunction-via-inhibition-of-apoptosis-and-necroptosis
#9
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/28844021/tlr2-tlr3-and-tlr5-regulation-of-pro-inflammatory-and-pro-labour-mediators-in-human-primary-myometrial-cells
#10
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be a significant global health care issue, due to our lack of understanding of the mechanisms that drive human labour and delivery. Toll-like receptors (TLRs) are essential in triggering an inflammatory response in human gestational tissues, leading to the production of pro-inflammatory and pro-labour mediators, and thus preterm birth. The aims of this study were to determine whether the adaptor molecules associated with TLR2, TLR3 and TLR5 signalling are involved in human myometrium...
August 24, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28836036/modulation-of-adenylate-cyclase-signaling-in-association-with-mkk3-6-stabilization-under-combination-of-sac-and-berberine-to-reduce-hepg2-cell-survivability
#11
Dipanwita Sengupta, Kaustav Dutta Chowdhury, Sujan Chatterjee, Avik Sarkar, Soumosish Paul, Pradip Kumar Sur, Gobinda Chandra Sadhukhan
Cancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated with S-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NFκβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition...
August 23, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28831401/global-screening-of-antiviral-genes-that-suppress-baculovirus-transgene-expression-in-mammalian-cells
#12
Chia-Hung Wang, Nenavath Gopal Naik, Lin-Li Liao, Sung-Chan Wei, Yu-Chan Chao
Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28817177/the-n-terminal-ubiquitin-associated-domain-of-cezanne-is-crucial-for-its-function-to-suppress-nf-%C3%AE%C2%BAb-pathway
#13
Yanxi Ji, Liu Cao, Lanyi Zeng, Zhen Zhang, Qiaoqiao Xiao, Penglin Guan, Shiyou Chen, Yu Chen, Min Wang, Deyin Guo
Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF-κB to attenuate NF-κB activation and to restrain pro-inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11-linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build-up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28816233/shikonin-induces-glioma-cell-necroptosis-in-vitro-by-ros-overproduction-and-promoting-rip1-rip3-necrosome-formation
#14
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/28811325/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#15
Luxi Chen, Yi Yuan, Shreya Kar, Madhu M Kanchi, Suruchi Arora, Ji E Kim, Pei F Koh, Einas Yousef, Ramar P Samy, Muthu K Shanmugam, Tuan Z Tan, Sung W Shin, Frank Arfuso, Han M Shen, Henry Yang, Boon C Goh, Joo I Park, Louis Gaboury, Peter E Lobie, Gautam Sethi, Lina Hk Lim, Alan P Kumar
Metastatic breast cancer is still remain incurable so far, new specifically targeted and more effective therapies for triple negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data has established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines which model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and Peroxisome Proliferator-Activated Receptor gamma (PPARγ)...
August 15, 2017: Molecular Cancer Therapeutics
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
#16
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
#17
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
#18
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
#19
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
#20
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
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