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https://www.readbyqxmd.com/read/28213559/an-organelle-rna-recognition-motif-protein-is-required-for-photosynthetic-subunit-psbf-transcript-editing
#1
Justin B Hackett, Xiaowen Shi, Amy T Kobylarz, Meriah K Lucas, Ryan L Wessendorf, Kevin M Hines, Stephane Bentolila, Maureen Hanson, Yan Lu
Loss-of-function mutations in Organelle RNA Recognition Motif Protein 6 (ORRM6) result in near absence of RNA editing of psbF-C77 and reduction in accD-C794 editing in Arabidopsis (Arabidopsis thaliana). The orrm6 mutants have decreased levels of PSII proteins, especially PsbF, lower PSII activity, pale green pigmentation, smaller leaf and plant sizes, and retarded growth. Stable expression of ORRM6 rescues orrm6 editing defects and mutant phenotype. Unlike ORRM1, the other known ORRM plastid editing factor, ORRM6 does not contain RNA editing interacting protein/multiple organellar RNA editing factor (RIP/MORF) boxes, which are required for ORRM1 to interact with site-specific pentatricopeptide repeat (PPR) protein editing factors...
February 17, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28186202/inhibition-of-receptor-interacting-protein-kinase-1-with-necrostatin-1s-ameliorates-disease-progression-in-elastase-induced-mouse-abdominal-aortic-aneurysm-model
#2
Qiwei Wang, Ting Zhou, Zhenjie Liu, Jun Ren, Noel Phan, Kartik Gupta, Danielle M Stewart, Stephanie Morgan, Carmel Assa, K Craig Kent, Bo Liu
Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s)...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176780/rip1-autophosphorylation-is-promoted-by-mitochondrial-ros-and-is-essential-for-rip3-recruitment-into-necrosome
#3
Yingying Zhang, Sheng Sean Su, Shubo Zhao, Zhentao Yang, Chuan-Qi Zhong, Xin Chen, Qixu Cai, Zhang-Hua Yang, Deli Huang, Rui Wu, Jiahuai Han
Necroptosis is a type of programmed cell death with great significance in many pathological processes. Tumour necrosis factor-α(TNF), a proinflammatory cytokine, is a prototypic trigger of necroptosis. It is known that mitochondrial reactive oxygen species (ROS) promote necroptosis, and that kinase activity of receptor interacting protein 1 (RIP1) is required for TNF-induced necroptosis. However, how ROS function and what RIP1 phosphorylates to promote necroptosis are largely unknown. Here we show that three crucial cysteines in RIP1 are required for sensing ROS, and ROS subsequently activates RIP1 autophosphorylation on serine residue 161 (S161)...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28151659/discovery-of-a-first-in-class-receptor-interacting-protein-1-rip1-kinase-specific-clinical-candidate-gsk2982772-for-the-treatment-of-inflammatory-diseases
#4
Philip A Harris, Scott B Berger, Jae U Jeong, Rakesh Nagilla, Deepak Bandyopadhyay, Nino Campobasso, Carol A Capriotti, Julie A Cox, Lauren Dare, Xiaoyang Dong, Patrick M Eidam, Joshua N Finger, Sandra J Hoffman, James Kang, Viera Kasparcova, Bryan W King, Ruth Lehr, Yunfeng Lan, Lara K Leister, John D Lich, Thomas T MacDonald, Nathan A Miller, Michael T Ouellette, Christina S Pao, Attiq Rahman, Michael A Reilly, Alan R Rendina, Elizabeth J Rivera, Michelle C Schaeffer, Clark A Sehon, Robert R Singhaus, Helen H Sun, Barbara A Swift, Rachel D Totoritis, Anna Vossenkämper, Paris Ward, David D Wisnoski, Daohua Zhang, Robert W Marquis, Peter J Gough, John Bertin
RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28151467/augmented-trophoblast-cell-death-in-preeclampsia-can-proceed-via-ceramide-mediated-necroptosis
#5
Liane Jennifer Bailey, Sruthi Alahari, Andrea Tagliaferro, Martin Post, Isabella Caniggia
Preeclampsia, a serious hypertensive disorder of pregnancy, is characterized by elevated ceramide (CER) content that is responsible for heightened trophoblast cell death rates via apoptosis and autophagy. Whether trophoblast cells undergo necroptosis, a newly characterized form of regulated necrosis, and the potential role of CER in this process remain to be established. Herein, we report that exposure of both JEG3 cells and primary isolated cytotrophoblasts to C16:0 CER in conjunction with a caspase-8 inhibitor (Q-VD-OPh) promoted necroptotic cell death, as evidenced by increased expression and association of receptor-interacting protein kinases RIP1 and RIP3, as well as phosphorylation of mixed lineage kinase domain-like (MLKL) protein...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28139737/histone-h4-expression-is-cooperatively-maintained-by-ikk%C3%AE-and-akt1-which-attenuates-cisplatin-induced-apoptosis-through-the-dna-pk-rip1-iaps-signaling-cascade
#6
Ruixue Wang, Xuelian Zheng, Lei Zhang, Bin Zhou, Huaizhong Hu, Zhiping Li, Lin Zhang, Yong Lin, Xia Wang
While chromatin remodeling mediated by post-translational modification of histone is extensively studied in carcinogenesis and cancer cell's response to chemotherapy and radiotherapy, little is known about the role of histone expression in chemoresistance. Here we report a novel chemoresistance mechanism involving histone H4 expression. Extended from our previous studies showing that concurrent blockage of the NF-κB and Akt signaling pathways sensitizes lung cancer cells to cisplatin-induced apoptosis, we for the first time found that knockdown of Akt1 and the NF-κB-activating kinase IKKβ cooperatively downregulated histone H4 expression, which increased cisplatin-induced apoptosis in lung cancer cells...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115086/necroptosis-mediates-the-antineoplastic-effects-of-the-soluble-fraction-of-polysaccharide-from-red-wine-in-walker-256-tumor-bearing-rats
#7
Maria Carolina Stipp, Iglesias de Lacerda Bezerra, Claudia Rita Corso, Francislaine A Dos Reis Livero, Luiz Alexandre Lomba, Adriana Rute Cordeiro Caillot, Aleksander Roberto Zampronio, José Ederaldo Queiroz-Telles, Giseli Klassen, Edneia A S Ramos, Guilherme Lanzi Sassaki, Alexandra Acco
Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls...
March 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28108311/rip1-and-rip3-contribute-to-shikonin-induced-dna-double-strand-breaks-in-glioma-cells-via-increase-of-intracellular-reactive-oxygen-species
#8
Zijian Zhou, Bin Lu, Chen Wang, Zongqi Wang, Tianfei Luo, Meihua Piao, Fankai Meng, Guangfan Chi, Yinan Luo, Pengfei Ge
Shikonin has been reported to induce glioma cell death via necroptosis, a type of programmed necrosis primarily mediated by RIP1 and RIP3. Although RIP1 and RIP3 are found to regulate some features of necrosis such as energy depletion and cellular membrane disruption, it remains unclear whether RIP1 and RIP3 could modulate DNA double strand breaks (DSBs), which is a crucial event leading to chromatinolysis. In this study, we used glioma cell lines and mice model of xenograft glioma to investigate the roles of RIP1 and RIP3 in shikonin-induced DNA DSBs...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28088644/tert-butyl-hydroperoxide-t-bhp-induced-apoptosis-and-necroptosis-in-endothelial-cells-roles-of-nox4-and-mitochondrion
#9
Wenwen Zhao, Haitao Feng, Wen Sun, Kang Liu, Jin-Jian Lu, Xiuping Chen
Oxidative stress causes endothelial death while underlying mechanisms remain elusive. Herein, the pro-death effect of tert-butyl hydroperoxide (t-BHP) was investigated with low concentration (50μM) of t-BHP (t-BHPL) and high concentration (500μM) of t-BHP (t-BHPH). Both t-BHPL and t-BHPH induced endothelial cell death was determined. T-BHPL induced caspase-dependent apoptosis and reactive oxygen species (ROS) generation, which was inhibited by N-acetyl-L-cysteine (NAC). Furthermore, NADPH oxidase inhibitor diphenyleneiodonium (DPI), NOX4 siRNA, and NOX4 inhibitor GKT137831 reduced t-BHPL-induced ROS generation while mitochondrial respiratory chain inhibitors rotenone (Rot), 2-thenoyltrifluoroacetone (TTFA), and antimycin A (AA) failed to do so...
January 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28087739/tnf-signaling-through-rip1-kinase-enhances-sn38-induced-death-in-colon-adenocarcinoma
#10
Lucia Cabal-Hierro, Peter J O'Dwyer
: Elucidation of tumor necrosis factor (TNF)-directed mechanisms for cell death induction and maintenance of tumor growth has revealed a role for receptor-interacting protein kinases 1 and 3 (RIPK1/RIP1 and RIPK3/RIP3), components of the necrosome complex, as determinants of cell fate. Here the participation of TNF signaling was analyzed with regard to the cytotoxic action of different DNA damaging agents in a panel of colon cancer cells. While most of these cell lines were insensitive to TNF, combination with these drugs increased sensitivity by inducing cell death and DNA damage, especially in the case of the topoisomerase inhibitor SN38...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28065786/cisplatin-induced-necroptosis-in-tnf%C3%AE-dependent-and-independent-pathways
#11
Yanfang Xu, Hua-Bin Ma, Yu-Lu Fang, Zhi-Rong Zhang, Jing Shao, Mao Hong, Chao-Jun Huang, Jing Liu, Rui-Qing Chen
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28060376/induction-of-necroptotic-cell-death-by-viral-activation-of-the-rig-i-or-sting-pathway
#12
Suruchi N Schock, Neha V Chandra, Yuefang Sun, Takashi Irie, Yoshinori Kitagawa, Bin Gotoh, Laurent Coscoy, Astar Winoto
Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. To see how general the interplay between viruses and necroptosis is, we surveyed seven different viruses...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28059467/muty-dna-glycosylase-protects-cells-from-tumor-necrosis-factor-alpha-induced-necroptosis
#13
An Hue Vy Tran, Se Hee Han, Joon Kim, Francesca Grasso, Ye Sun Han
Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28055006/biliary-tract-instillation-of-a-smac-mimetic-induces-trail-dependent-acute-sclerosing-cholangitis-like-injury-in-mice
#14
Maria Eugenia Guicciardi, Anuradha Krishnan, Steven F Bronk, Petra Hirsova, Thomas S Griffith, Gregory J Gores
Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiopathogenesis characterized by fibrous cholangiopathy of large and small bile ducts. Systemic administration of a murine TNF-related apoptosis-inducing ligand (TRAIL) receptor agonist induces a sclerosing cholangitis injury in C57BL/6 mice, suggesting endogenous TRAIL may contribute to sclerosing cholangitis syndromes. Cellular inhibitor of apoptosis proteins (cIAP-1 and cIAP-2) are negative regulators of inflammation and TRAIL receptor signaling...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28004006/the-different-effects-of-atorvastatin-and-pravastatin-on-cell-death-and-parp-activity-in-pancreatic-nit-1-cells
#15
Ya-Hui Chen, Yi-Chun Chen, Chin-San Liu, Ming-Chia Hsieh
Statins have been widely used drugs for lowering low-density lipoprotein and for preventing heart attack and stroke. However, the increased risk for developing diabetes during extended stain use and the molecular mechanisms remain unclear. The objective of this study was to elucidate the signaling pathway and biological function between necrosis and autophagy induced by atorvastatin (AS) and pravastatin (PS). Here we observed that atorvastatin (AS) can increase intracellular reactive oxygen species (ROS) and induce necrotic cell death and autophagy in NIT-1 cells, whereas pravastatin (PS) does not cause ROS and cell death but also induces autophagy...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28000518/artemisinin-inhibits-inflammatory-response-via-regulating-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#16
Ke Si Wang, Junbo Li, Zhe Wang, Chunliu Mi, Juan Ma, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Xuejun Jin
Artemisinin, isolated from the Chinese plant Artemisia annua, has been used for many years to treat different forms of malarial parasites. In this study, we explored the anti-inflammatory activity of artemisinin and the underlying mechanism of this action. We demonstrated that the anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice. Then the artemisinin significantly inhibited the expression of NF-κB reporter gene induced by TNF-α in a dose-dependent manner. Artemisinin also inhibited TNF-α induced phosphorylation and degradation of IκBα, p65 nuclear translocation...
December 21, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27992216/discovery-of-a-highly-potent-selective-and-metabolically-stable-inhibitor-of-receptor-interacting-protein-1-rip1-for-the-treatment-of-systemic-inflammatory-response-syndrome
#17
Yan Ren, Yaning Su, Liming Sun, Sudan He, Lingjun Meng, Daohong Liao, Xiao Liu, Yongfen Ma, Chunyan Liu, Sisi Li, Hanying Ruan, Xiaoguang Lei, Xiaodong Wang, Zhiyuan Zhang
On the basis of its essential role in driving inflammation and disease pathology, cell necrosis has gradually been verified as a promising therapeutic target for treating atherosclerosis, systemic inflammatory response syndrome (SIRS), and ischemia injury, among other diseases. Most necrosis inhibitors targeting receptor-interacting protein 1 (RIP1) still require further optimization because of weak potency or poor metabolic stability. We conducted a phenotypic screen and identified a micromolar hit with novel amide structure...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#18
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27877081/p-selectin-mediated-lox-expression-promotes-insulinoma-growth-in-rip1-tag2-mice-by-increasing-tissue-stiffness
#19
Cuiling Qi, Jialin Li, Simei Guo, Mengshi Li, Yuanyuan Li, Jiangchao Li, Qianqian Zhang, Lingyun Zheng, Xiaodong He, Xiaoming Zheng, Yanli He, Lijing Wang, Bo Wei
P-selectin, a cell adhesion molecule, is an important member of the selectin family. Recent studies have shown that P-selectin deletion inhibits tumor growth in Rip1-Tag2 mice by suppressing platelet accumulation in tumor tissues. This study aimed to evaluate whether and how P-selectin affects tumor stiffness in Rip1-Tag2 mice. To explore the role of P-selectin in tissue stiffness, we demonstrated that tumor progression in Rip1-Tag2 mice was correlated with tissue stiffness using immunofluorescence and histological staining...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27875900/effects-of-necrostatin-1-an-inhibitor-of-necroptosis-and-its-inactive-analogue-nec-1i-on-basal-cardiovascular-function
#20
A Szobi, T Rajtik, A Adameova
Inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIP1) by necrostatin-1 (Nec-1) alleviates cardiac injury due to prevention of necroptotic cell death. Its inactive analogue necrostatin-1i (Nec-1i), lacking RIP1 activity, serves as a suitable control. It is unknown if these agents influence the heart function in the absence of damaging stimuli. For this purpose, we measured intraarterial blood pressure (systolic - sBP and diastolic - dBP) and ECG parameters after a bolus administration of Nec-1 and Nec-1i in rats during 30 min...
November 23, 2016: Physiological Research
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