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https://www.readbyqxmd.com/read/27867009/a-polar-and-nucleotide-dependent-mechanism-of-action-for-rad51-paralogs-in-rad51-filament-remodeling
#1
Martin R G Taylor, Mário Špírek, Chu Jian Ma, Raffaella Carzaniga, Tohru Takaki, Lucy M Collinson, Eric C Greene, Lumir Krejci, Simon J Boulton
Central to homologous recombination in eukaryotes is the RAD51 recombinase, which forms helical nucleoprotein filaments on single-stranded DNA (ssDNA) and catalyzes strand invasion with homologous duplex DNA. Various regulatory proteins assist this reaction including the RAD51 paralogs. We recently discovered that a RAD51 paralog complex from C. elegans, RFS-1/RIP-1, functions predominantly downstream of filament assembly by binding and remodeling RAD-51-ssDNA filaments to a conformation more proficient for strand exchange...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27856241/palmitate-induces-rip1-rip3-dependent-necrosis-via-mlkl-mediated-pore-formation-in-the-plasma-membrane-of-raw-264-7%C3%A2-cells
#2
Seong Keun Kim, Mihee Yun, Gimoon Seo, Ji-Young Lee, Seong-Beom Lee
We previously reported that palmitate induces receptor-interacting protein (RIP)1-dependent necrosis in RAW 264.7 macrophage cells. In response to death receptor stimuli, RIP1 is reported to activate RIP3, which causes the phosphorylation and translocation of mixed-lineage kinase domain-like (MLKL) protein to the plasma membrane, subsequent pore formation in the plasma membrane, and necrotic cell death. In the current study, we investigated the role of MLKL in palmitate-induced, RIP1/RIP3-dependent necrotic cell death in RAW 264...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27738385/cyld-promotes-tnf-%C3%AE-induced-cell-necrosis-mediated-by-rip-1-in-human-lung-cancer-cells
#3
Xing Lin, Qianshun Chen, Chen Huang, Xunyu Xu
Lung cancer is one of the most common cancers in the world. Cylindromatosis (CYLD) is a deubiquitination enzyme and contributes to the degradation of ubiquitin chains on RIP1. The aim of the present study is to investigate the levels of CYLD in lung cancer patients and explore the molecular mechanism of CYLD in the lung cancer pathogenesis. The levels of CYLD were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27732109/ischemia-reperfusion-injury-triggers-tnf%C3%AE-induced-necroptosis-in-rat-retina
#4
Cho Rong Kim, Jie Hyun Kim, Hae-Young Lopilly Park, Chan Kee Park
PURPOSE: A recent study revealed a novel form of cell death, termed necroptosis, or programmed necrosis. Previous research indicated that after ischemia-reperfusion (IR) injury to the retina, Tumor Necrosis Factor α (TNFα) is increased, which may activate necroptosis. This study observed macroglial cell activation, and in particular, astrocyte activation, after the release of TNFα and other necroptosis factors in the rat retina due to IR. MATERIALS AND METHODS: IR was induced in the retinas of adult male Sprague-Dawley rats by increasing the intraocular pressure to 160 mmHg and then allowing reperfusion...
October 12, 2016: Current Eye Research
https://www.readbyqxmd.com/read/27631783/klhdc10-deficiency-protects-mice-against-tnf%C3%AE-induced-systemic-inflammation
#5
Namiko Yamaguchi, Shiori Sekine, Isao Naguro, Yusuke Sekine, Hidenori Ichijo
Systemic inflammatory response syndrome (SIRS) is a form of fatal acute inflammation for which there is no effective treatment. Here, we revealed that the ablation of Kelch domain containing 10 (KLHDC10), which we had originally identified as an activator of Apoptosis Signal-regulating Kinase 1 (ASK1), protects mice against TNFα-induced SIRS. The disease development of SIRS is mainly divided into two stages. The early stage is characterized by TNFα-induced systemic necroptosis, a regulated form of necrosis mediated by Receptor-interacting protein (RIP) 1/3 kinases...
2016: PloS One
https://www.readbyqxmd.com/read/27616656/caspase-inhibition-prevents-tumor-necrosis-factor-%C3%AE-induced-apoptosis-and-promotes-necrotic-cell-death-in-mouse-hepatocytes-in%C3%A2-vivo-and-in%C3%A2-vitro
#6
Hong-Min Ni, Mitchell R McGill, Xiaojuan Chao, Benjamin L Woolbright, Hartmut Jaeschke, Wen-Xing Ding
How different cell death modes and cell survival pathways cross talk remains elusive. We determined the interrelation of apoptosis, necrosis, and autophagy in tumor necrosis factor (TNF)-α/actinomycin D (ActD) and lipopolysaccharide/D-galactosamine (GalN)-induced hepatotoxicity in vitro and in vivo. We found that TNF-α/ActD-induced apoptosis was completely blocked by a general caspase inhibitor ZVAD-fmk at 24 hours but hepatocytes still died by necrosis at 48 hours. Inhibition of caspases also protected mice against lipopolysaccharide/GalN-induced apoptosis and liver injury at the early time point, but this protection was diminished after prolonged treatment by switching apoptosis to necrosis...
October 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27521978/role-of-necroptosis-in-autophagy-signaling-during-hepatic-ischemia-and-reperfusion
#7
Jeong-Min Hong, Seok-Joo Kim, Sun-Mee Lee
Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as "programmed necrosis" that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R...
October 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27267809/smac-mimetic-triggers-necroptosis-in-pancreatic-carcinoma-cells-when-caspase-activation-is-blocked
#8
Sabine Hannes, Behnaz Ahangarian Abhari, Simone Fulda
Evasion of apoptosis represents a key mechanism of treatment resistance of pancreatic cancer (PC) and contributes to the poor prognosis of this cancer type. Here, we report that induction of necroptosis is an alternative strategy to trigger programmed cell death in apoptosis-resistant PC cells. We show that the second mitochondrial activator of caspases (Smac) mimetic BV6 that antagonizes inhibitor of apoptosis (IAP) proteins induces necroptosis in PC cells in which apoptosis is blocked by the caspase inhibitor zVAD...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27216862/protein-tyrosine-phosphatase-shp-1-resurgence-as-new-drug-target-for-human-autoimmune-disorders
#9
REVIEW
Yadhu Sharma, Samina Bashir, Puja Bhardwaj, Altaf Ahmad, Farah Khan
Recognition of self-antigen and its destruction by the immune system is the hallmark of autoimmune diseases. During the developmental stages, immune cells are introduced to the self-antigen, for which tolerance develops. The inflammatory insults that break the immune tolerance provoke immune system against self-antigen, progressively leading to autoimmune diseases. SH2 domain containing protein tyrosine phosphatase (PTP), SHP-1, was identified as hematopoietic cell-specific PTP that regulates immune function from developing immune tolerance to mediating cell signaling post-immunoreceptor activation...
August 2016: Immunologic Research
https://www.readbyqxmd.com/read/27080932/therapeutic-hypothermia-attenuates-tissue-damage-and-cytokine-expression-after-traumatic-brain-injury-by-inhibiting-necroptosis-in-the-rat
#10
Tao Liu, Dong-xu Zhao, Hua Cui, Lei Chen, Ying-hui Bao, Yong Wang, Ji-yao Jiang
Necroptosis has been shown as an alternative form of cell death in many diseases, but the detailed mechanisms of the neuron loss after traumatic brain injury (TBI) in rodents remain unclear. To investigate whether necroptosis is induced after TBI and gets involved in the neuroprotecton of therapeutic hypothermia on the TBI, we observed the pathological and biochemical change of the necroptosis in the fluid percussion brain injury (FPI) model of the rats. We found that receptor-interacting protein (RIP) 1 and 3, and mixed lineage kinase domain-like protein (MLKL), the critical downstream mediators of necroptosis recently identified in vivo, as well as HMGB1 and the pro-inflammation cytokines TNF-α, IL-6 and IL-18, were increased at an early phase (6 h) in cortex after TBI...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27049944/the-necrosome-promotes-pancreatic-oncogenesis-via-cxcl1-and-mincle-induced-immune-suppression
#11
Lena Seifert, Gregor Werba, Shaun Tiwari, Nancy Ngoc Giao Ly, Sara Alothman, Dalia Alqunaibit, Antonina Avanzi, Rocky Barilla, Donnele Daley, Stephanie H Greco, Alejandro Torres-Hernandez, Matthew Pergamo, Atsuo Ochi, Constantinos P Zambirinis, Mridul Pansari, Mauricio Rendon, Daniel Tippens, Mautin Hundeyin, Vishnu R Mani, Cristina Hajdu, Dannielle Engle, George Miller
Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs...
April 14, 2016: Nature
https://www.readbyqxmd.com/read/27035122/receptor-interacting-protein-1-promotes-the-growth-and-invasion-in-gastric-cancer
#12
Guangwei Zhu, Jianxin Ye, Yongjian Huang, Wei Zheng, Jin Hua, Shugang Yang, Jinfu Zhuang, Jinzhou Wang
The receptor-interacting protein-1 (RIP-1) is an important molecular in inflammation signaling pathways, but the role of RIP-1 in gastric cancer is largely unknown. In this study, we tested the expression of RIP-1 in gastric cancer samples and analyzed the effects of expression of RIP-1 on the prognosis in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer cells and addressed the functional role of RIP-1 using a xenograft mouse model. A lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS cells...
June 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/26936927/promotion-of-homologous-recombination-by-sws-1-in-complex-with-rad-51-paralogs-in-caenorhabditis-elegans
#13
T Brooke McClendon, Meghan R Sullivan, Kara A Bernstein, Judith L Yanowitz
Homologous recombination (HR) repairs cytotoxic DNA double-strand breaks (DSBs) with high fidelity. Deficiencies in HR result in genome instability. A key early step in HR is the search for and invasion of a homologous DNA template by a single-stranded RAD-51 nucleoprotein filament. The Shu complex, composed of a SWIM domain-containing protein and its interacting RAD51 paralogs, promotes HR by regulating RAD51 filament dynamics. Despite Shu complex orthologs throughout eukaryotes, our understanding of its function has been most extensively characterized in budding yeast...
May 2016: Genetics
https://www.readbyqxmd.com/read/26912071/smac-mimetic-sensitizes-renal-cell-carcinoma-cells-to-interferon-%C3%AE-induced-apoptosis
#14
Michael Reiter, Ines Eckhardt, Axel Haferkamp, Simone Fulda
The prognosis of metastatic or relapsed renal cell carcinoma (RCC) is still very poor, highlighting the need for new treatment strategies. Here, we identify a cooperative antitumor activity of interferon-α (IFNα) together with the Smac mimetic BV6 that antagonizes antiapoptotic IAP proteins. BV6 and IFNα act together to reduce cell viability and to induce apoptosis in various RCC cell lines. Molecular studies revealed that BV6/IFNα co-treatment triggers apoptosis independently of autocrine/paracrine Tumor Necrosis Factor (TNF)α signaling, since the TNFα-blocking antibody Enbrel fails to rescue cell death...
May 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/26747710/loss-of-neutral-ceramidase-protects-cells-from-nutrient-and-energy-deprivation-induced-cell-death
#15
Kumaran Sundaram, Andrew R Mather, Subathra Marimuthu, Parag P Shah, Ashley J Snider, Lina M Obeid, Yusuf A Hannun, Levi J Beverly, Leah J Siskind
Sphingolipids are a family of lipids that regulate the cell cycle, differentiation and cell death. Sphingolipids are known to play a role in the induction of apoptosis, but a role for these lipids in necroptosis is largely unknown. Necroptosis is a programmed form of cell death that, unlike apoptosis, does not require ATP. Necroptosis can be induced under a variety of conditions, including nutrient deprivation and plays a major role in ischaemia/reperfusion injury to organs. Sphingolipids play a role in ischaemia/reperfusion injury in several organs...
March 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/26693068/necrostatin-1-reduces-intestinal-inflammation-and-colitis-associated-tumorigenesis-in-mice
#16
Zhen-Yu Liu, Bo Wu, Yun-Shan Guo, Ying-Hui Zhou, Zhi-Guang Fu, Bao-Qing Xu, Jiang-Hua Li, Lin Jing, Jian-Li Jiang, Juan Tang, Zhi-Nan Chen
Necroptosis, a novel form of programmed cell death, was recently shown to be strongly associated with intestinal inflammation in mice and in pediatric patients with inflammatory bowel disease (IBD). Persistent inflammation of the colon is an important risk factor for colorectal cancer. Necrostatin-1 (Nec-1), known as a specific inhibitor of necroptosis, through preventing the receptor-interacting protein (RIP) 1 and RIP3 interaction. In the present study, the anti-inflammatory and antitumorigenic efficacy of necrostatin-1 was studied in mouse models of colitis and colitis-associated cancer (CAC)...
2015: American Journal of Cancer Research
https://www.readbyqxmd.com/read/26575016/differential-role-of-rip1-in-smac-mimetic-mediated-chemosensitization-of-neuroblastoma-cells
#17
COMPARATIVE STUDY
Sebastian Czaplinski, Behnaz Ahangarian Abhari, Alica Torkov, Dominik Seggewiß, Manuela Hugle, Simone Fulda
We explored the potential of Smac mimetics, which antagonize Inhibitor of Apoptosis (IAP) proteins, for chemosensitization of neuroblastoma (NB). Here, we report that Smac mimetics, e.g. BV6, prime NB cells for chemotherapeutics including the topoisomerase II inhibitor doxorubicin (DOX) and vinca alkaloids such as Vincristine (VCR), Vinblastine (VBL) and Vinorelbine (VNR). Additionally, BV6 acts in concert with DOX or VCR to suppress long-term clonogenic growth. While BV6 causes rapid downregulation of cellular IAP (cIAP)1 protein and nuclear factor-kappaB (NF-κB) activation, DOX/BV6- or VCR/BV6-induced apoptosis occurs independently of NF-κB or TNFα signaling, since overexpression of dominant-negative IκBα superrepressor or the Tumor Necrosis Factor (TNF)α-blocking antibody Enbrel fail to block cell death...
December 8, 2015: Oncotarget
https://www.readbyqxmd.com/read/26519037/synergistic-effect-of-apoptosis-and-necroptosis-inhibitors-in-cisplatin-induced-nephrotoxicity
#18
Vivian Regina Tristão, Edson A Pessoa, Renata Nakamichi, Luciana A Reis, Marcelo Costa Batista, Marcelino de Souza Durão Junior, Júlio Cesar Martins Monte
Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection...
January 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/26433827/fine-mapping-for-double-podding-gene-in-chickpea
#19
L Ali, A Deokar, C Caballo, B Tar'an, J Gil, W Chen, T Millan, J Rubio
For the first time, fine mapping for sfl locus was carried out using a battery of new STMS and SNP markers. The target region was delimited to 92.6 Kb where seven annotated genes were found that could be candidate genes for the simple/double podding trait in chickpea. Four recombinant inbred populations (RIP-1, RIP-7, RIP-11, and CPR-01) were used to map the double podding gene (sfl) in chickpea. In RIP-1, the gene was initially mapped on linkage group (LG) 6 between the two sequence-tagged microsatellite site (STMS) markers TA120 and TR1...
January 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/26417912/celecoxib-enhances-sorafenib-sildenafil-lethality-in-cancer-cells-and-reverts-platinum-chemotherapy-resistance
#20
Timothy Webb, Jori Carter, Jane L Roberts, Andrew Poklepovic, William P McGuire, Laurence Booth, Paul Dent
The present studies sought to determine whether the lethality of the drug combination [sorafenib + sildenafil] could be enhanced by the anti-inflammatory agent celecoxib, using ovarian cancer and other tumor cell lines as models. Also, in a dose dependent fashion celecoxib enhanced [sorafenib + sildenafil] lethality in multiple ovarian cancer cell lines. In a dose dependent fashion celecoxib enhanced the ability of [sorafenib + sildenafil] to reduce expression of multiple chaperone proteins in parallel with lower levels of the drug efflux pumps ABCB1 and ABCG2...
2015: Cancer Biology & Therapy
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