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https://www.readbyqxmd.com/read/27877081/p-selectin-mediated-lox-expression-promotes-insulinoma-growth-in-rip1-tag2-mice-by-increasing-tissue-stiffness
#1
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
#2
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
https://www.readbyqxmd.com/read/27869161/therapeutic-targeting-of-necroptosis-by-smac-mimetic-bypasses-apoptosis-resistance-in-acute-myeloid-leukemia-cells
#3
C Safferthal, K Rohde, S Fulda
Resistance to apoptosis, for example due to overexpression of Inhibitor of Apoptosis (IAP) proteins, is associated with poor prognosis in acute myeloid leukemia (AML). Here, we identify that Smac mimetics such as BV6, which antagonizes IAP proteins, elicit necroptosis in AML cells, in which apoptosis is inhibited pharmacologically by caspase inhibitors or genetically by caspase-8 knockdown. Importantly, BV6 triggers necroptosis also in apoptosis-resistant patient-derived AML blasts, underlining the clinical relevance of our findings...
November 21, 2016: Oncogene
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
#4
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/27847551/caspase-3-deletion-promotes-necrosis-in-atherosclerotic-plaques-of-apoe-knockout-mice
#5
Mandy O J Grootaert, Dorien M Schrijvers, Marthe Hermans, Viviane O Van Hoof, Guido R Y De Meyer, Wim Martinet
Apoptosis of macrophages and vascular smooth muscle cells (VSMCs) in advanced atherosclerotic plaques contributes to plaque progression and instability. Caspase-3, a key executioner protease in the apoptotic pathway, has been identified in human and mouse atherosclerotic plaques but its role in atherogenesis is not fully explored. We therefore investigated the impact of caspase-3 deletion on atherosclerosis by crossbreeding caspase-3 knockout (Casp3(-/-)) mice with apolipoprotein E knockout (ApoE(-/-)) mice...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27798861/antiangiogenic-therapy-in-pancreatic-neuroendocrine-tumors
#6
REVIEW
Monica Capozzi, Claudia VON Arx, Chiara DE Divitiis, Alessandro Ottaiano, Fabiana Tatangelo, Giovanni Maria Romano, Salvatore Tafuto
In recent years, many progresses have been pursued in the management of advanced pancreatic neuroendocrine tumor (pNET); most of them were prompted by increasing knowledge of biology of these neoplasms, including the identification of promising biological targets for therapy. PNETs belong to a group of rare neoplastic diseases. They originate from neuroendocrine system cells and are very heterogeneous regarding anatomic localization and aggressiveness. Recently, many efforts have been particularly focused on the identification of pathologic pathways and innovative drugs in order to treat patients with unresectable, metastatic disease, in progressive well-differentiated pNETs...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27796641/fruit-preferential-activity-of-the-tomato-rip1-gene-promoter-in-transgenic-tomato-and-arabidopsis
#7
Priyanka Agarwal, Rahul Kumar, Amit Pareek, Arun K Sharma
Isolation and functional characterization of tissue- and stage-specific gene promoters is beneficial for genetic improvement of economically important crops. Here, we have characterized a putative promoter of a ripening-induced gene RIP1 (Ripening induced protein 1) in tomato. Quantification of the transcript level of RIP1 showed that its expression is fruit preferential, with maximum accumulation in red ripe fruits. To test the promoter activity, we made a reporter construct by cloning 1450 bp putative RIP1 promoter driving the GUS (ß-glucuronidase) gene expression and generated stable transgenic lines in tomato and Arabidopsis...
October 27, 2016: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/27795420/pivotal-role-of-rip1-and-mlkl-in-neuronal-cell-death-induced-by-the-human-neuroinvasive-coronavirus-oc43
#8
Mathieu Meessen-Pinard, Alain Le Coupanec, Marc Desforges, Pierre J Talbot
: Human coronaviruses (HCoV) are respiratory pathogens with neuroinvasive, neurotropic and neurovirulent properties, highlighting the importance to study the potential implication of these viruses in neurological diseases. The OC43 strain (HCoV-OC43) was reported to induce neuronal cell death which may participate in neuropathogenesis. Here, we show that HCoV-OC43 harboring two point mutations in the spike glycoprotein (rOC/Us183-241) was more neurovirulent than the wild-type HCoV-OC43 (rOC/ATCC) in mice and induced more cell death in murine and human neuronal cells...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27756752/tsc2-deficiency-unmasks-a-novel-necrosis-pathway-that-is-suppressed-by-the-rip1-rip3-mlkl-signaling-cascade
#9
Piotr T Filipczak, Cynthia L Thomas, Wenshu Chen, Andrew Salzman, Jacob D McDonald, Yong Lin, Steven A Belinsky
Tuberous sclerosis complex (TSC) is a genetic multi-organ disorder characterized by the development of neoplastic lesions in kidney, lung, brain, heart and skin. It is caused by an inactivating mutation in tumor suppressor genes coding the TSC1/TSC2 complex, resulting in hyperactivation of mTOR- and Raf/MEK/MAPK-dependent signaling that stimulates tumor cell proliferation and metastasis. Despite its oncogenic effect, cells with TSC deficiency were more sensitive to oxidative stress and dependent on mitochondrial metabolism, providing a rationale for a new therapeutic approach...
October 18, 2016: Cancer Research
https://www.readbyqxmd.com/read/27752362/simultaneous-induction-of-apoptosis-and-necroptosis-by-tanshinone-iia-in-human-hepatocellular-carcinoma-hepg2-cells
#10
C-Y Lin, T-W Chang, W-H Hsieh, M-C Hung, I-H Lin, S-C Lai, Y-J Tzeng
Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27748372/sensitizing-acute-myeloid-leukemia-cells-to-induced-differentiation-by-inhibiting-the-rip1-rip3-pathway
#11
J Xin, D You, P Breslin, J Li, J Zhang, W Wei, J Cannova, A Volk, R Gutierrez, Y Xiao, A Ni, G Ng, R Schmidt, Z Xia, J Pan, H Chen, M M Patel, P C Kuo, S Nand, A R Kini, J Zhang, J Chen, J Zhu, J Zhang
Tumor necrosis factor-α (TNF)-induced RIP1/RIP3-mediated necroptosis has been proposed to be an alternative strategy for treating apoptosis-resistant leukemia. However, we found that most acute myeloid leukemia (AML) cells, especially M4 and M5 subtypes, produce TNF and show basal level activation of RIP1/RIP3/MLKL signaling, yet do not undergo necroptosis. TNF, through RIP1/RIP3 signaling, prevents degradation of SOCS1, a key negative regulator of interferon-γ (IFN-γ) signaling. Using both pharmacologic and genetic assays, we show here that inactivation of RIP1/RIP3 resulted in reduction of SOCS1 protein levels and partial differentiation of AML cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27738385/cyld-promotes-tnf-%C3%AE-induced-cell-necrosis-mediated-by-rip-1-in-human-lung-cancer-cells
#12
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/27737687/lcl161-increases-paclitaxel-induced-apoptosis-by-degrading-ciap1-and-ciap2-in-nsclc
#13
Chengcheng Yang, Huangzhen Wang, Boxiang Zhang, Yimeng Chen, Yamin Zhang, Xin Sun, Guodong Xiao, Kejun Nan, Hong Ren, Sida Qin
BACKGROUND: LCL161, a novel Smac mimetic, is known to have anti-tumor activity and improve chemosensitivity in various cancers. However, the function and mechanisms of the combination of LCL161 and paclitaxel in non-small cell lung cancer (NSCLC) remain unknown. METHODS: Cellular inhibitor of apoptotic protein 1 and 2 (cIAP1&2) expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry. The correlations between cIAP1&2 expression and clinicopathological characteristics, prognosis were analyzed...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27732109/ischemia-reperfusion-injury-triggers-tnf%C3%AE-induced-necroptosis-in-rat-retina
#14
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/27703177/necrostatin-1-treatment-inhibits-osteocyte-necroptosis-and-trabecular-deterioration-in-ovariectomized-rats
#15
Hongwang Cui, Yongjun Zhu, Qiming Yang, Weikang Zhao, Shiyang Zhang, Ao Zhou, Dianming Jiang
Estrogen (E2) deficiency has been associated with accelerated osteocyte apoptosis. Our previous study showed necroptosis accelerated the loss of osteocytes in E2 deficiency-induced osteoporosis in rats in addition to apoptosis, but the mechanism involved remains. Necroptosis is a caspase-independent form of programmed cell death. In the necroptosis pathway, receptor interaction proteins 1 and 3 (RIP1/3) play vital roles. Necrostatin-1 (Nec-1) has been confirmed to be a specific inhibitor of necroptosis. However, the effect of Nec-1 on postmenopausal osteoporosis remains ambiguous...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27699664/rip1-upregulation-promoted-tumor-progression-by-activating-akt-bcl-2-bax-signaling-and-predicted-poor-postsurgical-prognosis-in-hcc
#16
Cong Wang, Bowen Yao, Meng Xu, Xin Zheng
Although growing body of evidences have identified a critical role for receptor-interacting protein kinase 1 (RIP1) in mediating cell death signaling, its possible contribution to hepatocellular carcinoma (HCC) progression remains unclear. Here, we displayed that expression of RIP1 was significantly upregulated in HCC tissues than in adjacent liver tissues from 81.9 % HCC patients (P < 0.001) by immunohistochemistry (IHC) staining. Overexpression of RIP1 was found positively associated with HBV infection, advanced TNM staging, portal vein invasion, and intrahepatic metastases...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27686451/dihydromyricetin-suppresses-tnf-%C3%AE-induced-nf-%C3%AE%C2%BAb-activation-and-target-gene-expression
#17
Nina Tang, Juan Ma, Ke Si Wang, Chunliu Mi, Ying Lv, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Jung Joon Lee, Xuejun Jin
Nuclear factor-kappa B (NF-κB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-κB inhibitor, dihydromyricetin, from the traditional herb Ampelopsis grossedentata, which has a long history of use in food and medicine. In this study, we demonstrated the effect of dihydromyricetin on NF-κB activation in TNF-α-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent nuclear translocation of p65...
November 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27685634/activation-of-necroptosis-in-human-and-experimental-cholestasis
#18
Marta B Afonso, Pedro M Rodrigues, André L Simão, Dimitry Ofengeim, Tânia Carvalho, Joana D Amaral, Maria M Gaspar, Helena Cortez-Pinto, Rui E Castro, Junying Yuan, Cecília M P Rodrigues
Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3(-/-)) mice subjected to common bile duct ligation (BDL)...
September 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27685625/tak1-regulates-caspase-8-activation-and-necroptotic-signaling-via-multiple-cell-death-checkpoints
#19
Xiaoyun Guo, Haifeng Yin, Yi Chen, Lei Li, Jing Li, Qinghang Liu
Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, although the underlying molecular regulatory mechanisms are not well defined. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8-mediated apoptotic signaling through both NFκB-dependent and -independent mechanisms...
September 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27685623/kinase-independent-function-of-rip1-critical-for-mature-t-cell-survival-and-proliferation
#20
John P Dowling, Yubo Cai, John Bertin, Peter J Gough, Jianke Zhang
The death receptor, Fas, triggers apoptotic death and is essential for maintaining homeostasis in the peripheral lymphoid organs. RIP1 was originally cloned when searching for Fas-binding proteins and was later shown to associate also with the signaling complex of TNFR1. Although Fas exclusively induces apoptosis, TNFR1 primarily activates the pro-survival/pro-inflammatory NF-κB pathway. Mutations in Fas lead to lymphoproliferative (lpr) diseases, and deletion of TNFR1 results in defective innate immune responses...
September 29, 2016: Cell Death & Disease
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