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https://www.readbyqxmd.com/read/29760953/hyperglycemia-potentiates-a-shift-from-apoptosis-to-rip1-dependent-necroptosis
#1
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/29731829/expression-of-receptor-interacting-protein-1-and-receptor-interacting-protein-3-oval-cells-in-a-rat-model-of-hepatocarcinogenesis
#2
Marta Wójcik, Ryszard Bobowiec, Urszula Lisiecka, Anna Śmiech
When apoptosis is suppressed in a neoplastic state, necroptosis may enable an anticancer response. In the present study, the association between apoptosis and necroptosis was assessed in a partial hepatectomy (PH)/diethylnitrosamine (DEN) rat model of hepatocarcinogenesis. Isolated oval cells (OCs) were analysed at 24, 48 and 72 h and at the first and second week of incubation. Phenotypic studies, apoptosis and necroptosis detection and proliferative activity assays were also performed on the OCs. The OCs were isolated from non-neoplastic (PH) and neoplastic (PH/DEN) livers, which expressed receptor interacting protein (RIP) 1 and RIP3...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29678581/molecular-and-histological-study-on-the-effects-of-non-thermal-irreversible-electroporation-on-the-liver
#3
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/29619976/ablative-hypofractionated-radiation-therapy-enhances-non-small-cell-lung-cancer-cell-killing-via-preferential-stimulation-of-necroptosis-in-vitro-and-in-vivo
#4
Huan-Huan Wang, Zhi-Qiang Wu, Dong Qian, Nicholas G Zaorsky, Ming-Han Qiu, Jing-Jing Cheng, Chao Jiang, Juan Wang, Xian-Liang Zeng, Chun-Lei Liu, Li-Jun Tian, Guo-Guang Ying, Mao-Bin Meng, Xi-Shan Hao, Zhi-Yong Yuan
PURPOSE: To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT). METHODS AND MATERIALS: Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29614353/necrosulfonamide-attenuates-the-spinal-cord-injury-via-necroptosis-inhibition
#5
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/29611115/c-elegans-based-screen-identifies-lysosome-damaging-alkaloids-that-induce-stat3-dependent-lysosomal-cell-death
#6
Yang Li, Yu Zhang, Qiwen Gan, Meng Xu, Xiao Ding, Guihua Tang, Jingjing Liang, Kai Liu, Xuezhao Liu, Xin Wang, Lingli Guo, Zhiyang Gao, Xiaojiang Hao, Chonglin Yang
Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway...
April 2, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29608987/rip1-and-rip3-contribute-to-shikonin-induced-glycolysis-suppression-in-glioma-cells-via-increase-of-intracellular-hydrogen-peroxide
#7
Bin Lu, Zongqi Wang, Ye Ding, Xuanzhong Wang, Shan Lu, Chongcheng Wang, Chuan He, Meihua Piao, Guangfan Chi, Yinan Luo, Pengfei Ge
RIP1 and RIP3 are necroptosis initiators, but their roles in regulation of glycolysis remain elusive. In this study, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression. Further investigation revealed that shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2 were significantly prevented when RIP1 or RIP3 was pharmacologically inhibited or genetically knocked down with SiRNA. Moreover, shikonin also triggered accumulation of intracellular H2 O2 and depletion of GSH and cysteine...
March 30, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29581256/puma-amplifies-necroptosis-signaling-by-activating-cytosolic-dna-sensors
#8
Dongshi Chen, Jingshan Tong, Liheng Yang, Liang Wei, Donna B Stolz, Jian Yu, Jianke Zhang, Lin Zhang
Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA , a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29557374/dabrafenib-an-inhibitor-of-rip3-kinase-dependent-necroptosis-reduces-ischemic-brain-injury
#9
Shelly A Cruz, Zhaohong Qin, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations...
February 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29550818/klotho-reduces-necroptosis-by-targeting-oxidative-stress-involved-in-renal-ischemic-reperfusion-injury
#10
Yingying Qian, Xiangjiang Guo, Lin Che, Xuejing Guan, Bei Wu, Renhua Lu, Mingli Zhu, Huihua Pang, Yucheng Yan, Zhaohui Ni, Leyi Gu
BACKGROUND/AIMS: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process. METHODS: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or H2O2. Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence...
March 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29546393/bufalin-inhibits-human-breast-cancer-tumorigenesis-by-inducing-cell-death-through-the-ros-mediated-rip1-rip3-parp-1-pathways
#11
Yanlan Li, Xiaodan Liu, Pengchao Gong, Xin Tian
Bufalin, a key active ingredient of the Chinese medicine Chan Su, inhibits breast cancer tumorigenesis in vitro and in vivo. Here we found that the pan-caspase inhibitor zVAD-fmk failed to inhibit bufalin-induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells, confirming that the cell death induced by bufalin is caspase-independent. Instead, bufalin increased the expression of the necroptosis mediators RIP1 and RIP3. Bufalin-induced cell death was prevented by small molecule inhibitors of RIP1 and poly (ADP-ribose) polymerase-1 (PARP-1) or genetic knockdown of RIP3 by shRNA transfection...
March 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29545181/necroptosis-associated-inhibition-of-insulin-like-growth-factor-1-receptor-attenuates-lps-induced-lung-injury
#12
Su Hwan Lee, Ju Hye Shin, Joo Han Song, Ah Young Leem, Moo Suk Park, Young Sam Kim, Joon Chang, Kyung Soo Chung
Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells. The levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, tumour necrosis factor-α, and macrophage inflammatory protein 2/C-X-C motif chemokine ligand 2 in the supernatant were significantly reduced in IGF-1 receptor siRNA-treated cells compared to control cells...
March 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29526761/type-i-immune-response-induces-keratinocyte-necroptosis-and-is-associated-with-interface-dermatitis
#13
Felix Lauffer, Manja Jargosch, Linda Krause, Natalie Garzorz-Stark, Regina Franz, Sophie Roenneberg, Alexander Böhner, Nikola S Mueller, Fabian J Theis, Carsten B Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Kilian Eyerich
Interface dermatitis is a characteristic histological pattern that occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different interface dermatitis positive skin diseases, lichen planus and lupus erythematosus. The shared transcriptome signature pointed toward a strong type I immune response, and biopsy-derived T cells were dominated by IFN-γ and tumor necrosis factor alpha (TNF-α) positive cells...
March 9, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29523873/rip3-is-an-upregulator-of-aerobic-metabolism-and-the-enhanced-respiration-by-necrosomal-rip3-feeds-back-on-necrosome-to-promote-necroptosis
#14
Xingfeng Qiu, Yingying Zhang, Jiahuai Han
No abstract text is available yet for this article.
May 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29518608/rip3-deficience-attenuates-potassium-oxonate-induced-hyperuricemia-and-kidney-injury
#15
Kang Wang, Lei Hu, Jian-Kang Chen
Recent preclinical and clinical evidence suggests that hyperuricemia (HU) is an independent risk factor for metabolic syndrome, hypertension, cardiovascular disease and chronic kidney disease. Receptor-interacting protein 3 (RIP3) is an important contributor in inducing programmed necrosis, representing a newly identified mechanism of cell death combining features of both apoptosis and necrosis. In our study, RIP3 was strongly expressed in mice with hyperuricemia. RIP3 deficiency attenuated hyperuricemia in mice, evidenced by reduced serum uric acid and creatinine and enhanced urinary uric acid and creatinine, as well as the improved histological alterations in renal sections...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29507626/sarcoma-targeting-peptide-decorated-polypeptide-nanogel-intracellularly-delivers-shikonin-for-upregulated-osteosarcoma-necroptosis-and-diminished-pulmonary-metastasis
#16
Suoyuan Li, Tao Zhang, Weiguo Xu, Jianxun Ding, Fei Yin, Jing Xu, Wei Sun, Hongsheng Wang, Mengxiong Sun, Zhengdong Cai, Yingqi Hua
PURPOSE: Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed. DESIGN: In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity...
2018: Theranostics
https://www.readbyqxmd.com/read/29496522/dihydrotanshinone-i-a-natural-product-ameliorates-dss-induced-experimental-ulcerative-colitis-in-mice
#17
Yanling Guo, Xiaxia Wu, Qin Wu, Yuanfu Lu, Jingshan Shi, Xiuping Chen
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the colon and rectum with increasing morbidity in recent years. 15,16-dihydrotanshinone Ӏ (DHT) is a natural product with multiple bioactivities. In this study, we aimed to investigate the protective effect and potential mechanisms of DHT on UC. Dextran sulfate sodium salt (DSS) was administrated in drinking water for 7 days to induce UC in mice. DHT (10 and 25 mg/kg) significantly alleviated DSS-induced body weight loss, disease activity index (DAI) scores, and improved histological alterations of colon tissues...
April 1, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29470982/rip3-deficiency-protects-against-traumatic-brain-injury-tbi-through-suppressing-oxidative-stress-inflammation-and-apoptosis-dependent-on-ampk-pathway
#18
Zai-Ming Liu, Qian-Xue Chen, Zhi-Biao Chen, Dao-Feng Tian, Ming-Chang Li, Jun-Min Wang, Long Wang, Bao-Hui Liu, Shen-Qi Zhang, Fei Li, Hui Ye, Long Zhou
Traumatic brain injury (TBI) is a leading cause of disability and mortality in young adults worldwide. The pathophysiology is not fully understood. Programmed necrosis (necroptosis) is a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Receptor-interacting protein 3 (RIP3) plays an important role in programmed necrosis. However, the effect of RIP3-related pathway in TBI is little to be known. We attempted to explore the significance of RIP3 in regulating TBI in vivo...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29464983/repurposing-anticancer-drugs-for-targeting-necroptosis
#19
Simone Fulda
Necroptosis represents a form of programmed cell death that can be engaged by various upstream signals, for example by ligation of death receptors, by viral sensors or by pattern recognition receptors. It depends on several key signaling proteins, including the kinases Receptor-Interacting Protein (RIP)1 and RIP3 and the pseudokinase mixed-lineage kinase domain-like protein (MLKL). Necroptosis has been implicated in a number of physiological and pathophysiological conditions and is disturbed in many human diseases...
April 25, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29436688/necrostatin-1-protects-c2c12-myotubes-from-cocl2-induced-hypoxia
#20
Rui Chen, Jiehua Xu, Yanling She, Ting Jiang, Shanyao Zhou, Huacai Shi, Cheng Li
Necrostatin-1 (Nec-1) is a selective and potent allosteric inhibitor of necroptosis by specifically inhibiting the activity of receptor‑interacting protein (RIP) 1 kinase. The aim of the present study was to determine the effect of Nec‑1 on an anoxia model comprising mouse skeletal C2C12 myotubes. In the present study, a hypoxic mimetic reagent, cobalt chloride (CoCl2), was used to induce hypoxia in C2C12 myotubes. The cytotoxic effects of CoCl2‑induced hypoxia were determined by a Cell Counting kit‑8 assay and flow cytometry...
May 2018: International Journal of Molecular Medicine
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