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https://www.readbyqxmd.com/read/29352268/cylindromatosis-mediates-neuronal-cell-death-in-vitro-and-in-vivo
#1
Goutham K Ganjam, Nicole Angela Terpolilli, Sebastian Diemert, Ina Eisenbach, Lena Hoffmann, Christina Reuther, Christiane Herden, Joachim Roth, Nikolaus Plesnila, Carsten Culmsee
The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29334122/inhibition-of-hsp90%C3%AE-protects-cultured-neurons-from-oxygen-glucose-deprivation-induced-necroptosis-by-decreasing-rip3-expression
#2
Zhen Wang, Li-Min Guo, Yong Wang, Hong-Kang Zhou, Shu-Chao Wang, Dan Chen, Ju-Fang Huang, Kun Xiong
Heat shock protein 90α (HSP90α) maintains cell stabilization and regulates cell death, respectively. Recent studies have shown that HSP90α is involved in receptor interacting protein 3 (RIP3)-mediated necroptosis in HT29 cells. It is known that oxygen and glucose deprivation (OGD) can induce necroptosis, which is regulated by RIP3 in neurons. However, it is still unclear whether HSP90α participates in the process of OGD-induced necroptosis in cultured neurons via the regulation of RIP3. Our study found that necroptosis occurs in primary cultured cortical neurons and PC-12 cells following exposure to OGD insult...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29330116/tnf-%C3%AE-increases-staphylococcus-aureus-induced-death-of-human-alveolar-epithelial-cell-line-a549-associated-with-rip3-mediated-necroptosis
#3
Shun-Hang Wen, Luo-Na Lin, Hu-Jun Wu, Lu Yu, Li Lin, Li-Li Zhu, Hai-Yan Li, Hai-Lin Zhang, Chang-Chong Li
AIM: To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN METHODS: The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus, where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses...
January 9, 2018: Life Sciences
https://www.readbyqxmd.com/read/29313217/temporal-pattern-and-crosstalk-of-necroptosis-markers-with-autophagy-and-apoptosis-associated-proteins-in-ischemic-hippocampus
#4
Fari Ryan, Fariba Khodagholi, Leila Dargahi, Dariush Minai-Tehrani, Abolhassan Ahmadiani
Necroptosis, a novel type of programmed cell death, has been recently implicated as a possible mechanism for cerebral ischemia-reperfusion (I/R) injury. We herein studied time-dependent changes of necroptosis markers along with apoptosis- and autophagy-associated proteins in rat hippocampus at 1, 3, 6, 12, 24, and 48 h after global cerebral I/R injury. Furthermore, to determine the cross talk between autophagy and necroptosis, we examined the effects of pretreatment with bafilomycin-A1 (Baf-A1), as a late-stage autophagy inhibitor, on necroptosis...
January 8, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29299822/necrostatin-1-protects-against-paraquat-induced-cardiac-contractile-dysfunction-via-rip1-rip3-mlkl-dependent-necroptosis-pathway
#5
Liping Zhang, Qiming Feng, Teng Wang
Paraquat is a highly toxic prooxidant that triggers oxidative stress and multi-organ failure including that of the heart. To date, effective treatment of paraquat toxicity is still not established. Necroptosis, a newly discovered form of programmed cell death, was recently shown to be strongly associated with cardiovascular disease. Receptor interaction proteins 1 (RIP1), receptor interaction proteins 3 (RIP3), and mixed lineage kinase domain like (MLKL) are key proteins in the necroptosis pathway. Necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis which acts by blocking the interaction between RIP1 and RIP3...
January 3, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29291399/the-release-of-microparticles-and-mitochondria-from-raw-264-7-murine-macrophage-cells-undergoing-necroptotic-cell-death-in-vitro
#6
Diane M Spencer, John R Dye, Claude A Pianatadosi, David S Pisetsky
Microparticles (MPs) are small membrane-bound vesicles released from activated or dying cells. As shown previously, LPS stimulation of the RAW 264.7 macrophage cell line can induce MP release, with the caspase inhibitor Z-VAD increasing the extent of this process. Since combined treatment of cells with LPS and Z-VAD can induce necroptosis, we explored particle release during this form of cell death using flow cytometry to assess particle size, binding of annexin V and staining for DNA with propidium iodide (PI) and SYTO 13...
December 29, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29274253/mir-200a-enhances-trail-induced-apoptosis-in-gastric-cancer-cells-by-targeting-a20
#7
Tianshu Guo, Ye Zhang, Xiujuan Qu, Xiaofang Che, Ce Li, Yibo Fan, Xing Wan, Rui Ma, Kezuo Hou, Huiming Zhou, Xiaowei He, Xuejun Hu, Yunpeng Liu, Ling Xu
Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) triggers apoptosis by inducing the death-inducing signaling complex (DISC) formation. Recently, TNFα-induced protein 3 (TNFAIP3, A20) was reported to prevent TRAIL-induced caspase 8 cleavage in the DISC by mediating ubiquitination of RIP1 in glioblastoma. However, whether A20 regulates caspase 8 cleavage in the DISC when TRAIL induces apoptosis in gastric cancer cells is unknown. In the present study, A20 interacted with RIP1 and DR4 in MGC803 and SGC7901 gastric cancer cells...
December 23, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29225581/protective-effect-of-unacylated-ghrelin-on-compression-induced-skeletal-muscle-injury-mediated-by-sirt1-signaling
#8
Felix N Ugwu, Angus P Yu, Thomas K Sin, Bjorn T Tam, Christopher W Lai, S C Wong, Parco M Siu
Unacylated ghrelin, the predominant form of circulating ghrelin, protects myotubes from cell death, which is a known attribute of pressure ulcers. In this study, we investigated whether unacylated ghrelin protects skeletal muscle from pressure-induced deep tissue injury by abolishing necroptosis and apoptosis signaling and whether these effects were mediated by SIRT1 pathway. Fifteen adult Sprague Dawley rats were assigned to receive saline or unacylated ghrelin with or without EX527 (a SIRT1 inhibitor). Animals underwent two 6-h compression cycles with 100 mmHg static pressure applied over the mid-tibialis region of the right limb whereas the left uncompressed limb served as the intra-animal control...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29175336/simultaneous-flow-cytometric-immunophenotyping-of-necroptosis-apoptosis-and-rip1-dependent-apoptosis
#9
H L Lee, R Pike, M H A Chong, A Vossenkamper, G Warnes
Flow cytometry was been widely used to measure apoptosis for many decades but the researcher has no definitive way of determining other forms of cell death using this technology. The use of Western Blot technology has numerous drawbacks in that all the cells in the sample whether live, dead or maybe undergoing multiple discrete forms of cell death are analysed as one population. Flow cytometry given that it can analyse different sub-populations of cells within a sample would reveal the expression of cell death markers within these sub-populations rather than just give a single result from the entire population...
November 23, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29175315/flagellin-increases-death-receptor-mediated-cell-death-in-a-rip1-dependent-manner
#10
Dora Hancz, Aniko Szabo, Tamás Molnar, Zsofia Varga, Aniko Hancz, Andrea Gregus, Anne-Odile Hueber, Eva Rajnavolgyi, Gabor Koncz
Efficient adjuvants have the potential to trigger both innate and adaptive immune responses simultaneously. Flagellin is a unique pathogen-derived protein, which is recognized by pattern recognition receptors (PRRs) as well as by B-cell and T cell receptors thus providing an important link between innate and adaptive immunity. The aforementioned properties define flagellin as an optimal adjuvant. The induction of immunogenic cell death could be an additional expectation for adjuvants in the context of cancer immunotherapy due to their ability to activate dendritic cells (DC) to present tumor antigens through the engulfment of dying cells...
January 2018: Immunology Letters
https://www.readbyqxmd.com/read/29170425/tradd-mediates-the-tumor-necrosis-factor-induced-apoptosis-of-l929-cells-in-the-absence-of-rip3
#11
Xixi Chang, Lili Wang, Zicheng Wang, Shuai Wu, Xiaoming Zhu, Shiping Hu, Yu Wang, Jiyun Yu, Guozhu Chen
Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) in L929 cells, so knockdown of RIP3 inhibits TNFα-induced L929 cell necroptosis. However, RIP3 knockdown was shown to switch TNFα-induced necroptosis to apoptosis in L929 cells in other studies. Therefore, whether RIP3 knockdown blocks the TNFα-induced death of L929 cells is controversial. In this study, TNFα activated caspase pathway and induced cell death in RIP3 knockdown L929 cells, and the RIP3-independent cell death had been blocked by Z-VAD-FMK (pan-caspase inhibitor) or caspase 8 knockdown, demonstrating that RIP3 knockdown switched TNFα-induced necroptosis to caspase-dependent apoptosis...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29170110/association-of-anti-her2-antibody-with-graphene-oxide-for-curative-treatment-of-osteosarcoma
#12
Lan Li, Chengke Luo, Zhenwei Song, Eduardo Reyes-Vargas, Fred Clayton, Jufang Huang, Peter Jensen, Xinjian Chen
The finding of HER2 overexpression in osteosarcoma (OS) makes HER2 a potential therapeutic target. However, studies indicate OS cells are nonresponsive to anti-HER2 antibody trastuzumab (TRA) therapy. We established stable, non-covalent association of TRA with nanomaterial graphene oxide (GO) to generated multivalent TRA/GO complexes that demonstrated markedly enhanced HER2-binding activity and capacity to rapidly kill OS cells. TRA/GO simultaneously induced oxidative stress and HER2 signaling in the target cells, leading to rapid depletion of the cellular inhibitors of apoptosis protein (cIAP) and caspase 8, formation of RIP1/RIPK3/MLKL necroptosome and necroptosis of the OS cells...
November 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29167229/embryonic-lethality-and-host-immunity-of-rela-deficient-mice-are-mediated-by-both-apoptosis-and-necroptosis
#13
Chengxian Xu, Xiaoxia Wu, Xixi Zhang, Qun Xie, Cunxian Fan, Haibing Zhang
In mammalian cells, signaling pathways triggered by TNF can be switched from NF-κB activation to apoptosis and/or necroptosis. The in vivo mechanisms underlying the mutual regulation of these three signaling pathways are poorly understood. In this article, we report that the embryonic lethality of RelA-deficient mice is partially prevented by the deletion of Rip3 or Mlkl, but it is fully rescued by the combined ablation of Fadd and Rip3 or Mlkl or by blocking RIP1 kinase activity (RIP1K45A). RelA-/-Fadd-/-Rip3-/- triple-knockout (TKO) and RelA-/-Rip1K45A/K45A mice displayed bacterial pneumonia leading to death ∼2 wk after birth...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29152118/sensitization-of-neuroblastoma-for-vincristine-induced-apoptosis-by-smac-mimetic-lcl161-is-attended-by-g2-cell-cycle-arrest-but-is-independent-of-nf%C3%AE%C2%BAb-rip1-and-tnf-%C3%AE
#14
Doerte Langemann, Magdalena Trochimiuk, Birgit Appl, Patrick Hundsdoerfer, Konrad Reinshagen, Georg Eschenburg
We demonstrated sensitization for chemotherapy by Smac mimetic (SM) LCL161, a potent antagonist of inhibitor of apoptosis proteins (IAP), in neuroblastoma (NB). Vinca alkaloids, particularly vincristine (VCR), displayed the strongest impact on inhibition of proliferation and apoptosis induction in combination with LCL161. The underlying signaling pathways remain elusive, though. LCL161 induces a quick degradation of cellular IAP 1 (cIAP-1). Combination of LCL161 with VCR had only marginal effects on X-linked IAP (XIAP) protein expression...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29142064/the-resurrection-of-the-piddosome-emerging-roles-in-the-dna-damage-response-and-centrosome-surveillance
#15
REVIEW
Valentina Sladky, Fabian Schuler, Luca L Fava, Andreas Villunger
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29131627/enhancement-of-9%C3%AE-hydroxy-4-androstene-3-17-dione-production-from-soybean-phytosterols-by-deficiency-of-a-regulated-intramembrane-proteolysis-metalloprotease-in-mycobacterium-neoaurum
#16
Liang-Bin Xiong, Wan-Ju Sun, Yong-Jun Liu, Feng-Qing Wang, Dong-Zhi Wei
Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, the SigD was identified as a negative factor of the 9-OHAD production in M. neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA and hsd4A) in the sterol catabolic pathway...
November 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29116428/bromoethylindole-bei-9-redirects-nf-%C3%AE%C2%BAb-signaling-induced-by-camptothecin-and-tnf%C3%AE-to-promote-cell-death-in-colon-cancer-cells
#17
Rupak Chowdhury, Dominique Gales, Paloma Valenzuela, Sonni Miller, Teshome Yehualaeshet, Upender Manne, Giulio Francia, Temesgen Samuel
Chemotherapeutic regimens containing camptothecin (CPT), 5-fluorouracil, and oxaliplatin are used to treat advanced colorectal cancer. We previously reported that an indole derivative, 3-(2-bromoethyl)indole (BEI-9), inhibited the proliferation of colon cancer cells and suppressed NF-κB activation. Here, we show that a combination of BEI-9 with either CPT or tumor necrosis factor alpha (TNFα) enhances cell death. Using colorectal cancer cells, we examined the activation of NF-κB by drugs, the potential of BEI-9 for inhibiting drug-induced NF-κB activation, and the enhancement of cell death by combination treatments...
November 8, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29075784/lippia-origanoides-extract-induces-cell-cycle-arrest-and-apoptosis-and-suppresses-nf-%C3%AE%C2%BAb-signaling-in-triple-negative-breast-cancer-cells
#18
Vishak Raman, Jorge Luis Fuentes Lorenzo, Elena E Stashenko, Morris Levy, Maria M Levy, Ignacio G Camarillo
Treatments targeting hormone receptors typically fail to provide a positive clinical outcome against triple-negative breast cancers (TNBC), which lack expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2/neu). Towards identifying viable treatments for aggressive breast cancer, we have tested an extract of the tropical plant Lippia origanoides (LOE) on TNBC and normal cells lines to uncover its potential anticancer effects. Treatment with LOE reduced TNBC cell viability in a dose-dependent manner to a greater extent than in normal mammary epithelial MCF10A cells...
December 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29021293/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#19
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 H K Lim, Alan P Kumar
Metastatic breast cancer is still 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 have 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 that model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and PPARγ...
August 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28993192/up-regulation-of-rip3-alleviates-cervical-cancer-progression-through-inducing-necroptosis
#20
Dong-Li Zhang, Gui-Xia Sun, Jun Tian, Hong-Xia Zhang
Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an important part of the cellular machinery, executing programmed necroptosis. However, the biological role and clinical significance of RIP3 in cervical cancer remains to be further elucidated. Here, we reported that RIP3 was expressed lowly in cervical cancer cell lines and clinical cervical tumor samples, along with the reduction of receptor-interacting protein 1 (RIP1) and p-mixed lineage kinase domain-like protein (MLKL). Further, we found that over-expressing RIP3 suppressed the proliferation and tumorigenicity of cervical cancer cells both in vitro and in vivo...
October 6, 2017: Biochemical and Biophysical Research Communications
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