beta Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase.

Su KH; Shyue SK; Kou YRChing LCChiang ANYu YBChen CYPan CCLee TS

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beta Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase.

机译：β共同整合了促红细胞生成素受体在激活内皮氮信号氧化合成酶。

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Erythropoietin (EPO), the key hormone for erythropoiesis, also increases nitric oxide (NO) bioavailability in endothelial cells (ECs), yet the definitive mechanisms are not fully understood. Increasing evidence has demonstrated that beta common receptor (betaCR) plays a crucial role in EPO-mediated non-hematopoietic effects. We investigated the role of betaCR in EPO-induced endothelial NO synthase (eNOS) activation in bovine aortic ECs (BAECs) and the molecular mechanisms involved. Results of confocal microscopy and immunoprecipitation analyses revealed that betaCR was colocalized and interacted with EPO receptor (EPOR) in ECs. Inhibition of betaCR or EPOR by neutralizing antibodies or small interfering RNA abolished the EPO-induced NO production. Additionally, blockage of betaCR abrogated the EPO-induced increase in the phosphorylation of eNOS, Akt, Src, or Janus kinase 2 (JAK2). Immunoprecipitation analysis revealed that treatment with EPO increased the interaction between betaCR and eNOS, which was suppressed by inhibition of Src, JAK2, or Akt signaling with specific pharmacological inhibitors. Furthermore, EPO-induced EC proliferation, migration, and tube formation were blocked by pretreatment with betaCR antibody and Src, JAK2, or PI3K/Akt inhibitors. Moreover, in vivo experiments showed that EPO increased the level of phosphorylated eNOS, Src, JAK2, and Akt, as well as betaCR-eNOS association in aortas and promoted the angiogenesis in Matrigel plug, which was diminished by betaCR or EPOR neutralizing antibodies. Our findings suggest that betaCR may play an integrative role in the EPO signaling-mediated activation of eNOS in ECs.

机译：促红细胞生成素(EPO)的关键激素红细胞生成,也会增加一氧化氮(NO)在内皮细胞(ECs),生物利用度的机制还没有完全理解。β共同受体(betaCR)扮演至关重要的作用在EPO-mediated non-hematopoietic效果。EPO-induced内皮没有合酶(以挪士)激活牛主动脉ECs (BAECs)和分子机制。共焦显微镜和免疫沉淀反应分析发现,betaCR与和ECs与促红细胞生成素受体(EPOR)。抑制betaCR或EPOR中和抗体或小干扰RNA废除了EPO-induced没有生产。betaCR废除EPO-induced增加一种蛋白激酶的磷酸化以挪士,Src,或者杰纳斯激酶2 (JAK2)。显示,促红细胞生成素治疗增加了betaCR之间的相互作用和以挪士抑制抑制的Src、JAK2或一种蛋白激酶信号与特定的药理抑制剂。增殖、迁移和管形成被预处理和betaCR抗体Src、JAK2或PI3K / Akt抑制剂。体内实验表明,促红细胞生成素的增加磷酸化水平以挪士,Src、JAK2和一种蛋白激酶,以及在主动脉和betaCR-eNOS协会促进了血管生成在基底膜基质插头,减少了betaCR还是EPOR中和抗体。在欧洲专利局发挥综合作用ECs signaling-mediated激活以挪士。

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《Journal of Cellular Physiology》 |2011年第12期|3330-3339|共10页
作者
Su KH; Shyue SK; Kou YRChing LCChiang ANYu YBChen CYPan CCLee TS;
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Department of Physiology, National Yang-Ming University, Taipei, Taiwan.;

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正文语种英语
中图分类细胞生物学;
关键词
Aorta; pipe formation; ErythropoiesisErythropoietinSmall Interfering RNANeutralizing AntibodiesErythropoietin ReceptorsNitric Oxide Synthase Type III;

机译：主动脉;管干扰RNANeutralizingAntibodiesErythropoietin ReceptorsNitric氧化合酶III型;

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1. Martentoxin, a large-conductance Ca2+-activated K+ channel inhibitor, attenuated TNF-α-induced nitric oxide release by human umbilical vein endothelial cells [J] . Jun Wang, Wenyi Qian, Qing Zhu, 生物医学研究杂志（英文版） . 2013,第005期
2. Martentoxin, a large-conductance Ca2＋-activated K＋ channel inhibitor, attenuated TNF-α-induced nitric oxide release by human umbilical vein endothelial cells [J] . Jun Wang, Wenyi Qian, Qing Zhu, 生物医学研究杂志：英文版 . 2013,第005期
3. 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focus on the nitric oxide pathwayAging395Heart failure with preserved ejection fraction develops when feeding western diet to senescence-accelerated mice396Cardiovascular markers as predictors of cognitive decline in elderly hypertensive patients397Changes in connexin43 in old rats with volume overload chronic heart failureGenetics and epigenetics400Calcium content in the aortic valve is associated with 1G>2G matrix metalloproteinase 1 polymorphism401Neuropeptide receptor gene s (NPSR1) polymorphism and sleep disturbances402Endothelin-1 gene Lys198Asn polymorphism in men with essential hypertension complicated and uncomplicated with chronic heart failure403Association of common polymorphisms of the lipoprotein lipase and pon1 genes with the metabolic syndrome in a sample of community participantsGenomics, proteomics, metabolomics, lipidomics and glycomics405Gene expression quantification using multiplexed color-coded probe pairs to determine RNA content in sporadic cardiac myxoma406Large-scale phosphorylation study of the type 2 diabetic heart subjected to ischemia / reperfusion injury407Transcriptome-based identification of new anti-inflammatory properties of the olive oil hydroxytyrosol in vascular endothelial cell under basal and proinflammatory conditions408Gene polymorphisms combinations and risk of myocardial infarctionComputer modelling, bioinformatics and big data411Comparison of the repolarization reserve in three state-of-the-art models of the human ventricular action potentialMetabolism, diabetes mellitus and obesity414Endothelial monocyte-activating polypeptide-II improves heart function in type -I Diabetes mellitus415Admission glucose level is independent predictor of impaired left ventricular function in patients with acute myocardial infarction: a two dimensional speckle-tracking echocardiography study416Association between biochemical markers of lipid profile and inflammatory reaction and stiffness of the vascular wall in hypertensive patients with abdominal obesity417Multiple common co-morbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress and myocardial stiffening418Investigating the cardiovascular effects of antiretroviral drugs in a lean and high fat/sucrose diet rat model of obesity419Statins in the treatment of non-alcoholic steatohepatitis (NASH). 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V Garcia-Martinez, C Lopez Sanchez, W Hamed, 2016

机译：早期心脏腔室specification291Bmp2期间海报会议2Morphogenetic mechanisms290MiR-133调控对视黄酸途径在早期心脏具有或不具有2型糖尿病mellitus295Association循环的α2B肾上腺素受体基因插入/缺失多态性的缺失等位基因和高血压的formationDevelopmental genetics294Association通过的miR-130调节心房分化陷波的作用：Vascular298Gamma分泌酶抑制剂阻止增殖和动脉导管未闭的迁移平滑肌细胞 - 内源性大麻素1型受体（CNR1）与冠状动脉疾病（CAD）的2型糖尿病mellitusCell生长，分化和干细胞的G1359A多态性的在出生后的闭合信令导管arteriosus299Mesenchymal基质状从诱导的多能干细胞（iPS）衍生的单元（MLC）细胞：有希望的治疗选项，以促进neovascularization300Sonic刺猬促进间充质干细胞分化为vascula ř平滑肌细胞cardiovacsular disease301Proinflammatory细胞因子分泌和在内皮细胞中表观遗传学修饰处理的LPS-GinfivalisCell死亡和细胞凋亡 - Vascular304Mitophagy充当针对人血管平滑肌细胞中的保障机制凋亡诱导动脉粥样硬化lipidsTranscriptional控制和RNA种类 - 在Vascular307MicroRNA-34a的作用利用后缺氧内皮cells310Specific循环微RNA水平的血管injury309Long非编码RNA景观临床适用的方法衰减新内膜形成与miR-146a的抑制剂的血管calcification308Local递送关联与高血压，高血糖和功能失调的HDL在急性冠状动脉综合征patientsCytokines和细胞炎症 - Vascular313Phosphodiesterase5A向上调控血管内皮促炎性条件下进行：为ω-3polyunsaturated aatty酸二十二碳六acid31一个新公开的抗炎活性4Cardiovascular风险修改与超低剂量抗细胞因子药物在人M-CSF的巨噬细胞的类风湿arthritis315Conversion成泡沫细胞降低了其经典M1偏振activation316Lymphocytic心肌炎具有增加斑块炎症和在冠状动脉中的斑块出血一致时，促进心肌infarction317Serum骨保护素水平的促炎性应答通过抑制手段Heart323A新的合成肽对肥大体外 - predictsdeclined众多患者的代谢syndromeGrowth因子和神经激素循环内皮 - 衍生的细胞和单核衍生的祖细胞 - 胃泌素释放肽（GRP）对血管inflammationSignal转导的Vascular320Effect p38的α图激酶nfkb324Inducible成纤维细胞特异性敲除是在异丙基肾上腺素诱导的心脏hypertrophy325Regulation的小鼠模型中的心脏保护β-肾上腺素受体诱发由抑制性肌力响应ORY G蛋白，腺苷酸环化酶同种型5,6和phosphodiesterases326Binding到RGS3和M2毒蕈碱性乙酰胆碱受体调制的刺激p190RhoGAP的翻译后修饰，parylation和脱乙酰化中LMNA的心脏myocytes327Cardiac调节底物特异性扩张的心肌病小鼠model328Beta肾上腺素能调节所述b56delta / PP2A全酶在心肌细胞通过b56delta磷酸化丝氨酸573Nitric氧化物和活性氧 - Vascular331Oxidative应激诱导的miR-200c的破坏SIRT1，FOXO1和eNOS332Antioxidant疗法防止氧化应激诱导内皮功能障碍和提高之间的调节环路伤口Healing333Morphological和在冠状动脉diseaseCytoskeleton红细胞和机械传导的生化特征 - Heart336Novel肌球蛋白的活化剂，JSH化合物，ratsExtracellular矩阵增加心肌收缩力没有变时作用和纤维化 - 的Vascular339Ablation Toll样受体9通过衰减增殖和心脏fibroblasts340Altered血管在因子VII小鼠后肢缺血模型重塑活化蛋白酶（FSAP）deficiencyVasculogenesis，血管生成和proly的arteriogenesis343Pro血管生成作用的分化导致心肌梗死后心脏破裂羟化酶抑制剂及其在用于冠状动脉总occlusion344Nrf2驱动治疗性血管生成的新颖的策略的使用潜在的血管生成转录非依赖性方式：氧化应激response345Angiogenic基因治疗的主调节器的新功能，尽管高效血管生长，不能改善上在鼠后肢侧支血管生长PAR-1抑制的毛细动脉和shunting346Effect在含氧量正常或慢性缺血性后肢的兔肌肉功能-Role model347Quaking是内皮细胞分化的关键调节剂，新血管形成和angiogenesis348在鸡胚绒毛尿囊膜（CAM）“新兴血管生成”。一种不同于心肌祖细胞体内study349Exosomes和间充质干细胞刺激血管生成的体外和GRK2的体内经由EMMPRINEndothelium352Reciprocal调节和血管舒缓激肽受体刺激调制的Ca 2+的细胞内骨的内皮cells353The角色形态发生蛋白9和10在内皮炎症和atherosclerosis354The贡献水平GPR55在分离的人将L-α-溶血磷脂酰肌醇诱导的血管舒张肺arteries355The内皮保护ACE抑制剂Zofenoprilat通过H2S production356A类新的糖模拟药物发挥抗炎活性，以防止游离脂肪酸诱导的内皮dysfunction357Endothelial祖细胞凋亡的内皮细胞从降低喷射fractionheart failure358Proosteogenic基因保留衍生微粒配给differentiatesas在患者的胸主动脉aneurysm359Endothelin ETB REC内皮细胞活化通过经由PI3Kg的对cAMP调节，在动脉的作用IP3 receptors363A新颖功能的激活诱导的钙振荡eptors调解放松来自患有心血管疾病（CVD）的平滑肌和pericytes362CX3CR1阳性髓样细胞在心包阻力动脉到胰岛素应答调节血管平滑肌紧张壁增生，通过平滑肌细胞proliferation364NRP1和NRP2的调制内膜增生的发展vivo365Azithromycin诱导自噬在主动脉平滑肌cellsCoagulation，血栓形成和platelets368The实时血小板依赖性醛固酮促血栓形成作用的体内评价mice369Development玩的方法的重要作用用于体内在mice370The活性血栓的检测抗血小板的血小板聚集和腺苷的人类platelets372Regulation的功能状态肝素抗凝药物的牛磺酸chloramine371The影响结构类似物的效果二磷酸酯的释放通过d二聚体在急性冠状动脉综合征（体外研究）氧传感，局部缺血和脑缺血reperfusion376Abscisic酸的小鼠模型reperfusion375Sirtuin 5介导的脑损伤：在从局部缺血心肌保护的新播放ultramicronized十六酰胺乙醇的377Protective效果（？ PEA-UM）在干细胞衍生的心肌细胞的vivo378Identification心肌缺血再灌注损伤的使用心脏特异性标志物，并在这些细胞中的额外的测试模拟缺血/再灌注system379Single剂量静脉二甲双胍治疗能买得起在受伤大鼠肾脏的显著保护的长效用于慢性阻塞性肺disease381Dependence抗氧化潜力上的缺血 - 再灌注的生理参数，细胞凋亡和超微结构氨基acids382The冲击浓度毒蕈碱性受体拮抗剂缺血reperfusion380Cardiotoxicity的实验模型兔心肌实验aterosclerosisMitochondria和energetics385MicroRNA-1在正常线粒体钙单向转运体（MCU）的依赖性调节和肥大hearts386Mitochondrial稳态和心脏保护：在糖尿病heart388NO结蛋白和线粒体融合蛋白-2 AB-crystallin387Overexpression（Mfn2的）和相关的线粒体功能障碍共同目标依赖性预防通透性转换孔（MPTP）的开口由H 2 S和其在大鼠心脏mitochondria389G蛋白偶联受体的Ca 2+积累的调节激酶2（GRK2）是在回收曝光后线粒体形态和功能于电离辐射（IR）性别issues392Sex差异基本在肺血管的控制;注重与射血分数一氧化氮pathwayAging395Heart失败开发当馈送西方饮食到衰老加速mice396Cardiovascular标志物的中老年大鼠与体积连接蛋白43在老年高血压patients397Changes认知衰退的预测过载慢性心脏failureGenetics和epigenetics400Calcium内容在主动脉瓣与1G相关联> 2G矩阵男性高血压并发和不复杂的与脂蛋白脂肪酶的常见多态性与PON1基因的慢性心脏failure403Association与代谢综合征金属蛋白酶1个polymorphism401Neuropeptide受体基因S（NPSR1）多态性与睡眠disturbances402Endothelin-1基因Lys198Asn多态性社区participantsGenomics，蛋白质组学，代谢组样品中使用复用颜色编码的探针对脂质组学和glycomics405Gene表达定量，以确定在经受的橄榄油的新抗炎性质基于injury407Transcriptome-缺血/再灌注鉴定2型糖尿病心脏的零星心脏myxoma406Large规模磷酸化研究RNA含量羟基酪醇在血管内皮细胞在人类心室动作potentialMetabolism，糖尿病三个国家的最先进的车型在基础和促炎conditions408Gene多态性组合和心肌infarctionComputer建模，生物信息学和复极储备的大data411Comparison的风险细胞和单核细胞obesity414Endothelial激活多肽-II型糖尿病-I mellitus415Admission葡萄糖水平改善心脏功能的左心室功能受损患者急性心肌梗死的独立预测因子：二维斑点追踪超声心动图脂质谱和炎症反应，在高血压患者腹部obesity417Multiple常见共病血管壁的刚度的生化标志物之间ýstudy416Association产生左心室冠状动脉微血管功能障碍，氧化应激和心肌stiffening418Investigating的抗逆转录病毒药物的心血管作用有关的舒张功能障碍贫和高脂肪/非酒精性脂肪性肝炎（NASH）的治疗obesity419Statins的蔗糖饮食大鼠模型。我们在康斯坦察县2年的前瞻性研究经验，Romania420Epicardial脂肪组织心血管结果的ACS患者接受PCI？动脉及肺动脉hypertension423Dependence心脏节律disorers和ACE基因ID多态性与高血压patients424Molecular机制背后的有益预测在TGF-β轴和在人类升主动脉中prehypertension427Vascular微循环和大循环异常aneurysms426Early迹象肾素 - 血管紧张素系统的动作的肺动脉hypertension425Inhibition尿皮质素2的影响平滑肌细胞表达的血管tone428Cardiac铁2控制和血管重塑在开发在一个新颖的猪modelBiomarkers431Arrhythmogenic心肌病慢性血栓栓塞性肺动脉高压：一个新的，非侵入性的biomarker432Can循环微RNA区分类型1和类型2心肌梗塞433Design的高通量含多处？前蛋白质组学测定，以确定左室舒张功能障碍diabetes434Monocyte衍生和P-选择携带微粒不同由低脂肪饮食的患者心血管危险因素谁将会和谁不会被开发宽度评估心血管event435Red血细胞分布修改在慢性心脏failure436Invasive和患者的治疗低温对脑的水平心房fibrillation437The效果射频诱导的心脏去神经支配的质量的非侵入性评价薄膜的多色干涉显微镜中的血清衍生的神经营养因子（BDNF）以下心肺resustitation438Novel生物标志物来预测结果患者心脏衰竭和冠状动脉graftingInvasive，非侵入性和分子imaging443Diet组成的影响Ø链接抑郁和焦虑心血管disease440Troponins和肌红蛋白动态重度主动脉瓣stenosis439Biological因素n中的鼠ob突变的基因分型，：心脏功能，宏观和微观循环和使用IV-OCT定量分析猪冠状动脉和兔子主动脉的病变的肝steatosis444Characterization的微超声表征：与histologyGene疗法和细胞相关性therapy447Enhancing存活和小鼠心房间充质cells448VCAM-1在实验性心肌梗塞表达及其与骨髓来源的单核细胞retentionTissue engineering451Advanced多层支架增加干细胞衍生的工程改造的心脏组织的人类cardiomyocytes452Response的成熟到模拟缺血/再灌注的血管生成潜力急性高血糖conditions453Serum白蛋白水凝胶的存在防止新生儿cardiomyocytes454A新颖画笔技术的去分化为低粘度的转印紫外光可固化青色甲基丙烯酸酯上的盐水浸没在体外羊心脏

beta Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase.

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