共查询到20条相似文献，搜索用时 0 毫秒
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Human NDR1/STK38 belongs to the nuclear‐Dbf2‐related (NDR) family of Ser/Thr kinases. It has been implicated to function in centrosome duplication, control of cell cycle and apoptosis. However, the mechanism of NDR1 signaling pathway remains largely elusive. Here, we report a novel role of NDR1 in NF‐κB activation. By overexpression, NDR1 potentiates NF‐κB activation induced by TNFα, whereas knockdown of NDR1 expression inhibits NF‐κB activation induced by TNFα. Coimmunoprecipitation shows that NDR1 interacts with multiple signal components except p65 in NF‐κB signaling pathway. Furthermore, both phosphorylation and kinase dead mutants of NDR1 lose their synergistic effects on TNFα‐induced NF‐κB activation. siRNA oligo against NDR1 and kinase dead mutant as well mainly block the NF‐κB activation induced by TRAF2 but not RIP1. Furthermore, kinase dead mutant of NDR1 fails to interact with TRAF2. Taken together, our findings suggest an unknown function of NDR1, which may regulate NF‐κB activation by its kinase activity. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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Renli Qi Jinxiu Huang Qi Wang Hong Liu Ruisheng Wang Jing Wang Feiyun Yang 《Journal of cellular physiology》2018,233(2):1236-1246
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Mark D. Namba Yonatan M. Kupchik Sade M. Spencer Constanza Garcia‐Keller Julianna G. Goenaga Gregory L. Powell Ian A. Vicino Ian B. Hogue Cassandra D. Gipson 《Addiction biology》2020,25(5)
Nicotine self‐administration is associated with decreased expression of the glial glutamate transporter (GLT‐1) and the cystine‐glutamate exchange protein xCT within the nucleus accumbens core (NAcore). N‐acetylcysteine (NAC) has been shown to restore these proteins in a rodent model of drug addiction and relapse. However, the specific molecular mechanisms driving its inhibitory effects on cue‐induced nicotine reinstatement are unknown. Here, we confirm that extinction of nicotine‐seeking behavior is associated with impaired NAcore GLT‐1 function and expression and demonstrates that reinstatement of nicotine seeking rapidly enhances membrane fraction GLT‐1 expression. Extinction and cue‐induced reinstatement of nicotine seeking was also associated with increased tumor necrosis factor alpha (TNFα) and decreased glial fibrillary acidic protein (GFAP) expression in the NAcore. NAC treatment (100 mg/kg/day, i.p., for 5 d) inhibited cue‐induced nicotine seeking and suppressed AMPA to NMDA current ratios, suggesting that NAC reduces NAcore postsynaptic excitability. In separate experiments, rats received NAC and an antisense vivo‐morpholino to selectively suppress GLT‐1 expression in the NAcore during extinction and were subsequently tested for cue‐induced reinstatement of nicotine seeking. NAC treatment rescued NAcore GLT‐1 expression and attenuated cue‐induced nicotine seeking, which was blocked by GLT‐1 antisense. NAC also reduced TNFα expression in the NAcore. Viral manipulation of the NF‐κB pathway, which is downstream of TNFα, revealed that cue‐induced nicotine seeking is regulated by NF‐κB pathway signaling in the NAcore independent of GLT‐1 expression. Ultimately, these results are the first to show that immunomodulatory mechanisms may regulate known nicotine‐induced alterations in glutamatergic plasticity that mediate cue‐induced nicotine‐seeking behavior. 相似文献
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Hyunju Kim Yu‐Ran Na So Yeon Kim Eun Gyeong Yang 《Journal of cellular biochemistry》2016,117(3):647-658
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Human non‐small cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Estrogenic signals have been suggested to be important for the growth and metastasis of NSCLC cells. Our present data showed that estrogen‐related receptor alpha (ERRα), while not ERRβ or ERRγ, was significantly elevated in NSCLC cell lines as compared with that in normal bronchial epithelial cell line BEAS‐2B. The expression of ERRα in clinical NSCLC tissues was significantly greater than that in their matched normal adjacent tissues. Over expression of ERRα can trigger the proliferation, migration, and invasion of NSCLC cells, while si‐ERRα or ERRα inhibitor showed opposite effects. ERRα can increase the mRNA and protein expression of IL‐6, while not IL‐8, IL‐10, IL‐22, VEGF, TGF‐β, or TNF‐α, in NSCLC cells. Silence of IL‐6 attenuated ERRα induced proliferation and cell invasion. Furthermore, our data revealed the inhibition of NF‐κB, while not ERK1/2 or PI3K/Akt, abolished ERRα induced production of IL‐6. This might be due to that overexpression of ERRα can increase the expression and nuclear translocation of p65 in NSCLC cells. Collectively, our data showed that activation of NF‐κB/IL‐6 is involved in ERRα induced migration and invasion of NSCLC cells. It suggested that ERRα might be a potential target for NSCLC treatment. 相似文献
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Hsi‐Kai Tsou Chen‐Ming Su Hsien‐Te Chen Ming‐Han Hsieh Cheng‐Jyh Lin Dah‐Yuu Lu Chih‐Hsin Tang Yi‐Hung Chen 《Journal of cellular biochemistry》2010,109(6):1244-1253
Tumor necrosis factor‐α (TNF‐α) is a pleiotropic cytokine produced by activated macrophages. Nitric oxide (NO) is a highly reactive nitrogen radical implicated in inflammatory responses. We investigated the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and NO production stimulated by TNF‐α in cultured myoblasts. TNF‐α stimulation caused iNOS expression and NO production in myoblasts (G7 cells). TNF‐α‐mediated iNOS expression was attenuated by integrin‐linked kinase (ILK) inhibitor (KP392) and siRNA. Pretreatment with Akt inhibitor, mammalian target of rapamycin (mTOR) inhibitor (rapamycin), NF‐κB inhibitor (PDTC), and IκB protease inhibitor (TPCK) also inhibited the potentiating action of TNF‐α. Stimulation of cells with TNF‐α increased ILK kinase activity. TNF‐α also increased the Akt and mTOR phosphorylation. TNF‐α mediated an increase of NF‐κB‐specific DNA–protein complex formation, p65 translocation into nucleus, NF‐κB‐luciferase activity was inhibited by KP392, Akt inhibitor, and rapamycin. Our results suggest that TNF‐α increased iNOS expression and NO production in myoblasts via the ILK/Akt/mTOR and NF‐κB signaling pathway. J. Cell. Biochem. 109: 1244–1253, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
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Qingchun Lei Huan Gu Lei Li Tingting Wu Wentao Xie Meizhang Li Ninghui Zhao 《Journal of cellular and molecular medicine》2020,24(1):530-538
As a malignant tumour of the central nervous system, glioma exhibits high incidence and poor prognosis. Although TNIP1 and the TNF‐α/NF‐κB axis play key roles in immune diseases and inflammatory responses, their relationship and role in glioma remain unknown. Here, we revealed high levels of TNIP1 and TNF‐α/NF‐κB in glioma tissue. Glioma cell proliferation was activated with TNF‐α treatment and showed extreme sensitivity to the TNF receptor antagonist. Furthermore, loss of TNIP1 disbanded the A20 complex responsible for IκB degradation and NF‐κB nucleus translocation, and consequently erased TNFα‐induced glioma cell proliferation. Thus, our investigation uncovered a vital function of the TNIP1‐mediated TNF‐α/NF‐κB axis in glioma cell proliferation and provides novel insight into glioma pathology and diagnosis. 相似文献
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Chen Shen Wang Ma Lei Ding Songtao Li Xiaobing Dou Zhenyuan Song 《Journal of cellular and molecular medicine》2018,22(7):3572-3581
Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non‐alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be clearly elucidated. Toll‐like receptor (TLR) 4 plays a fundamental role in activating the innate immune system. Intriguingly, hepatocytes express TLR4 and machinery for TLR4 signalling pathway. That liver‐specific TLR4 knockout mice are protective against diet‐induced NAFLD suggests that hepatocyte TLR4 signalling pathway plays an important role in NAFLD pathogenesis. Herein, using cultured hepatocytes, we sought to directly examine the role of TLR4 signalling pathway in palmitate‐elicited hepatotoxicity and to elucidate underlying mechanism(s). Our data reveal that palmitate exposure up‐regulates TLR4 expression at both mRNA and protein levels in hepatocytes, which are associated with NF‐κB activation. The inhibition of TLR4 signalling pathway through both pharmacological and genetic approaches abolished palmitate‐induced cell death, suggesting that TLR4 signalling pathway activation contributes to palmitate‐induced hepatotoxicity. Mechanistic investigations demonstrate that inositol‐requiring enzyme 1α (IRE1α), one of three major signal transduction pathways activated during endoplasmic reticulum (ER) stress, is the downstream target of palmitate‐elicited TLR4 activation and mechanistically implicated in TLR4 activation‐triggered cell death in response to palmitate exposure. Collectively, our data identify that the TLR4‐IRE1α pathway activation contributes to palmitate‐elicited lipotoxicity in hepatocytes. Our findings suggest that targeting TLR4‐IRE1α pathway can be a potential therapeutic choice for the treatment of NAFLD as well as other metabolic disorders, with lipotoxicity being the principal pathomechanism. 相似文献
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Tao Zhang Shuai Guo Xinying Zhu Jinxia Qiu Ganzhen Deng Changwei Qiu 《Journal of cellular and molecular medicine》2020,24(15):8430-8440
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Tengfei Song Tao Lin Jun Ma Lei Guo Ling Zhang Xuhui Zhou Tianwen Ye 《Journal of cellular and molecular medicine》2018,22(10):4738-4750
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Lu Zhang Hualing Sun Jing Zhang Fangfang Song Liyuan Huang Zhengguo Cao Cui Huang 《Journal of cellular and molecular medicine》2020,24(14):7939-7948
Cementum regeneration, as one of the most difficult challenges of periodontal regeneration, is influenced by inflammatory factors. Inflammation may hamper or promote periodontal tissue repair under different circumstances, as it is found to do in dentin‐pulp complex and bone tissue. Our team demonstrated that YAP promotes mineralization of OCCM, a cementoblast cell line. However, the effect of YAP on its mineralization under inflammatory microenvironment is unclear. In this study, cementogenesis in vitro was up‐regulated after transient TNF‐α treatment for 30 minutes. YAP expression also was increased by TNF‐α treatment. YAP overexpression promoted OCCM mineralization after the cells were transiently treated with TNF‐α because YAP overexpression inhibited NF‐κB pathway activity, while YAP knockdown elevated it. The inhibited mineralization potential and activated NF‐κB pathway activity by YAP knockdown also were partly rescued by the application of the NF‐κB inhibitor Bay 11‐7082. These results demonstrated that YAP plays a positive role in the mineralization of TNF‐α transiently treated cementoblast, partly by inhibiting the NF‐κB pathway activity. 相似文献
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Qiu‐Fang Gao Xiu‐Hong Zhang Feng‐Lai Yuan Ming‐Dong Zhao Xia Li 《Cell biology international》2016,40(12):1340-1348
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Selda Gezginci‐Oktayoglu Sehnaz Bolkent Boran Bertan Bayrak Refiye Yanardag 《Cell biology international》2010,34(5):543-552
This study was designed to evaluate the effect of Z‐FA.FMK (benzyloxycarbonyl‐l ‐phenylalanyl‐alanine‐fluoromethylketone), a pharmacological inhibitor of cathepsin B, on the proliferation of duodenal mucosal epithelial cells and the cellular system that controls this mechanism in these cells in vivo. For this investigation, BALB/c male mice were divided into four groups. The first group received physiological saline, the second group was administered Z‐FA.FMK, the third group received d ‐GalN (d ‐galactosamine) and TNF‐α (tumour necrosis factor‐α) and the fourth group was given both d ‐GalN/TNF‐α and Z‐FA.FMK. When d ‐GalN/TNF‐α was administered alone, we observed an increase in IL‐1β‐positive and active NF‐κB‐positive duodenal epithelial cells, a decrease in PCNA (proliferative cell nuclear antigen)‐positive duodenal epithelial cells and an increase in degenerative changes in duodenum. On the other hand, Z‐FA.FMK pretreatment inhibited all of these changes. Furthermore, lipid peroxidation, protein carbonyl and collagen levels were increased, glutathione level and superoxide dismutase activity were decreased, while there was no change in catalase activity by d ‐GalN/TNF‐α injection. On the contrary, the Z‐FA.FMK pretreatment before d ‐GalN/TNF‐α blocked these effects. Based on these findings, we suggest that Z‐FA.FMK might act as a proliferative mediator which is controlled by IL‐1β through NF‐κB and oxidative stress in duodenal epithelial cells of d ‐GalN/TNF‐α‐administered mice. 相似文献