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萝卜硫素通过src/PI3K/Akt通路调控人脐静脉内皮细胞NO的生成机制

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中国医院药学杂志 2021年第24期41卷 2526-2529页

作者：刘萌芽史礼君李金鑫许杜娟蔡邦荣刘改枝河南中医药大学河南郑州450046

目的:研究萝卜硫素(SFN)促进人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)生成一氧化氮(NO),参与内皮细胞修复的作用机制。方法:采用MTT法检测SFN对HUVEC细胞存活率的影响;检测SFN对HUVEC NO释放量的影响;采用Weste... 详细信息

目的:研究萝卜硫素(SFN)促进人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)生成一氧化氮(NO),参与内皮细胞修复的作用机制。方法:采用MTT法检测SFN对HUVEC细胞存活率的影响;检测SFN对HUVEC NO释放量的影响;采用Western blot法检测SFN对NO释放途径相关蛋白表达量的影响。结果:SFN浓度低于50μmol·L-1时,对HUVEC细胞无明显毒性(Psrc激酶的活化。结论:SFN通过src/PI3K/Akt信号通路增强HUVEC细胞中eNOS的活性,促进NO生成参与内皮细胞修复,为SFN在预防内皮功能障碍、动脉粥样硬化和其他心血管疾病方面的应用提供实验依据。

关键词：萝卜硫素 src Akt 一氧化氮合酶一氧化氮人脐静脉内皮细胞

Viral proteins and src family kinases: Mechanisms of pathogenicity from a “liaison dangereuse”

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World Journal of Virology 2013年第2期2卷 71-78页

作者： Mario Angelo Pagano Elena Tibaldi Giorgio Palù Anna Maria Brunati Department of Molecular Medicine University of Padua

To complete their life cycle and spread, viruses interfere with and gain control of diverse cellular processes, this most often occurring through interaction between viral proteins(VPs) and resident protein partners. Among the latter, src family kinases(SFKs), a class of non-receptor tyrosine kinases that contributes to the conversion of extracellular signals into intracellular signaling cascades and is involved in virtually all cellular processes, have recently emerged as critical mediators between the cell's infrastructure and the viral demands. In this scenario, structural or ex novo synthesized VPs are able to bind to the different domains of these enzymes through specific short linear motifs present along their sequences. Proline-rich motifs displaying the conserved minimal consensus PxxP and recognizing the SFK src homology(SH)3 domain constitute a cardinal signature for the formation of multiprotein complexes and this interaction may promote phosphorylation of VPs by SFKs, thus creating phosphotyrosine motifs that become a docking site for the SH2 domains of SFKs or other SH2 domain-bearing signaling molecules. Importantly, the formation of these assemblies also results in a change in the activity and/or location of SFKs, and these events are critical in perturbing key signalingpathways so that viruses can utilize the cell's machinery to their own benefit. In the light of these observations, although VPs as such, especially those with enzyme activity, are still regarded as valuable targets for therapeutic strategies, multiprotein complexes composed of viral and host cell proteins are increasingly becoming objects of investigation with a view to deeply characterize the structural aspects that favor their formation and to develop new compounds able to contrast viral diseases in an alternative manner.

关键词： Interaction Phosphotyrosine Proline-rich motif src homology 2 domain src homology 3 domain

Inhibition of src Kinase Attenuates Neuroinflammation and Protects Dopaminergic Neurons in Parkinson's Disease Models

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神经药理学报 2019年第4期 43-44页

作者： YANG Han-yu WANG Lu ZANG Cai-xia WANG Yue SHANG Jun-mei BAO Xiu-qi WANG Xiao-liang ZHANG Dan State Key Laboratory of Natural Products and Functions Department of PharmacologyInstitute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College

Background:Chronic neuroinflammation plays an important role in the pathogenesis of Parkinson's disease( PD). During the process of neuroinflammation,over-activated microglia release many pro-inflammatory factors,which eventually induce neurodegeneration. Inhibition of excessive microglial activation is regarded as a promisingstrategy for PD treatment. src is a non-receptor tyrosine kinase and its role is mostly reported to be related to tumors. Recently,some reports indicated that src is a central mediator in multiple signaling pathways including neuroinflammation. Objective:The aim of the present study was to demonstrate the role of src in microglial regulation and neuroinflammation. Methods:The lipopolysaccharide( LPS)-stimulated BV-2 microglia in vitro model and the classic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine( MPTP)-induced in vivo PD model were applied to evaluate the effect of src inhibition on neuroinflammation,neuron survival and PD motor symptom. Western blot analysis was used to measure the protein expression. Immunocytochemistry assay was used to measure the protein expression and cell morphology. Immunohistochemistry assay was used to observe pathological change. qRT-PCR analysis was used to measure the mRNA expression. Griess method was used to measure NO concentration in cell cultures. The rotarod test is used to measure coordinated motor skills. Results:The results showed that inhibition of src could significantly relieve microgliosis and decrease levels of inflammatory factors both in vitro and in vivo. src inhibition significantly reduced protein expressions of iNOS and COX2 and decrease mRNA expressions of TNF-α,and IL-6 in both LPS-stimulated BV-2 microglia and MPTP-treated mice. We also found that src is critical for microglia to exert neurotoxic effect. SH-SY5 Y cell viability was dramatically reduced after incubating with conditioned medium from LPS-treated BV2 cells,and the morphological change of SH-SY5 Y cells could be observed. src

关键词： src microglia neuroinflammation Parkinson’s disease neuroprotection BV2 cells

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正常小鼠src法敏感药物评价标准研究

中国肿瘤临床 1990年第5期17卷 273-275页

作者：宁连胜王垣孙慧王庆生赵骁军石强安秀梅苏明秀赵文华毛慧生侯子正天津市肿瘤研究所实验肿瘤研究室天津市肿瘤研究所流行病研究室

目前,国内外不同实验室采用的正常小鼠src法检测化疗药物敏感标准,差异甚大。对其测定的准确性和临床符合率不无影响。本文根据我室1986年8月～1989年6月间,测定女性乳腺癌对化疗药物敏感性64例为资料,研究如何规定src法中化疗药物敏感... 详细信息

目前,国内外不同实验室采用的正常小鼠src法检测化疗药物敏感标准,差异甚大。对其测定的准确性和临床符合率不无影响。本文根据我室1986年8月～1989年6月间,测定女性乳腺癌对化疗药物敏感性64例为资料,研究如何规定src法中化疗药物敏感标准更为合理。方法学:(1)将全部实验数据输入微机,计算每例的△TS值、消退率和P值;(2)按17种标准,计算在每个标准下对每种药物的敏感率;(3)得出的結果与已知每种药物的有效率比较,并进行统计学处理。结果发现:(1)女性乳腺癌对化疗药物的敏感率,随评价标准不同而发生变化,规定的标准高(严),敏感率低,反之则高;(2)当采用P+|15％|的标准时,与临床已知的结果相一致,R=0.8,V=4,P<0.05。因此,通过本分析,采用P+|15％|标准时,较为合理。

关键词： src 药物敏感标准抗癌药物

Integrin CD11b attenuates colitis by strengthening src-Akt pathway to polarize anti-inflammatory IL-10 expression

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Integrin CD11b attenuates colitis by strengthening Src-Akt p...

Effects of Low Level Lead Exposure on Brain Barriers:Role of Activation of Nonreceptor Tyrosine Kinase src

第十一届全国免疫学学术大会

作者： Xiang Hu Kewei Qin Hua Zhang Tianliang Li Nan Li Xuetao Cao Chaofeng Han National Key Laboratory of Medical Molecular Biology & Department of Immunology Institute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical Sciences National Key Laboratory of Medical Immunology & Institute of Immunology Second Military Medical University

Purpose:To investigate whether CD11 b and its signaling can control autoimmunity via IL-10 ***:The colitis model was induced by *** were assay by Q-PCR or *** transduction was detected by ***:CD11 b deficient(Itgam-/-) mice were more susceptible to DSS-induced colitis,with more TNF-α while less IL-10 ***11 b inhibited NF-κB while promoted AP-1 activation through activating src,leading to decreased TNF-α while increased IL-10 *** interacted with and promoted c-Cbl-mediated degradation of the inhibitory subunit p85 of PI3 ***,src inhibitor dasatinibaggravated DSS-induced colitis by decreasing IL-10 while increasing TNF-α in ***,CD11 b promotes IL-10 production by activating src-Aktsignal ***:An axis of CD11b-src pathway is important in balancing homeostasis of TLR-induced pro-inflammatory and anti-inflammatory responses.

关键词： CD11b Toll-like receptor IL-10 src Colitis

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Effects of Low Level Lead Exposure on Brain Barriers:Role of...

2016中国毒理学会神经毒理专业委员会学术年会

作者：宋晗郑刚沈学锋刘新秦骆文静陈景元第四军医大学军事预防医学院劳动与环境卫生教研室

Background Lead（Pb）,as a widespread environmental pollutant,is known to cause a wide range of neurotoxic effects,including decreased intelligence quotient,cognitive deficits,poor attention span,and increased *** has long been recognized as a neurodevelopmental *** blood-brain barrier（BBB） and blood-cerebrospinal fluid barrier（BCB） are known to be targets of Pb neurotoxicity. Brain capillary endothelial cells with tight junctions（TJs） between adjacent cells, astrocyte end feet, and pericytes within the capillary basement constitute the structural basis of the BBB. Choroid plexus epithelial cells with tight junctions（TJs） between adjacent cells constitute the structural basis of the ***, the underlying mechanisms of Pb-induced reduction of TJ proteins of BBB and BCB are still *** way Pb enters into the brain parenchyma or cerebrospinal fluid can be classified into two categories: intercellular regions after breakdown TJ proteins and Pb transporter in the endothelial/epithelial cell bodies. Recently, hemichannels of Connexin 43（Cx43）, the most ubiquitously expressed gap junction proteins in the BBB and BCB, were found to be important pathways for many substances. In previous study, Cx43 expression was enhanced in the hippocampus, a major target of Pb-induced neurotoxicity, implying that Pb may accumulate in the hippocampus via Cx43 *** is nonreceptor protein tyrosine kinases that mediates the integrin signaling on the focal adhesion complex at the cell-toextracellular matrix interface. src kinase activity is required for both assembly and disassembly of TJ proteins in different epithelial cells. In addition, src has long been known to interact with and phosphorylate Cx43 to promote downregulation of GJ communication and cause GJ disassembly,even channel closure. src phosphorylation was found to increase greater than other kinases in brain microvessels after Pb exposure by using a phosphoprotein antibody *** This

关键词： Lead BBB BCB src TJ occludin GRP78 GJ Cx43 iZCx43

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加权src算法在伪装人脸识别中的应用

系统工程理论与实践 2011年第S2期31卷 124-128页

作者：甘俊英肖娟五邑大学信息工程学院江门529020

针对伪装人脸识别问题,基于稀疏表示分类法(sparse representation-based classification,src)鲁棒性好的特性,分析了src算法,探讨了该算法存在的问题:稀疏解不够稀疏.提出了一种加权src模型,即在src模型基础上增加一个权值.结合Homotop... 详细信息

针对伪装人脸识别问题,基于稀疏表示分类法(sparse representation-based classification,src)鲁棒性好的特性,分析了src算法,探讨了该算法存在的问题:稀疏解不够稀疏.提出了一种加权src模型,即在src模型基础上增加一个权值.结合Homotopy算法获得了更理想、更稀疏的解.基于AR数据库的实验结果表明,加权src算法的识别率随权值的变化而变化,拥有比src算法更高的正确识别率.

关键词：稀疏表示伪装人脸识别 src 加权src

体外src蛋白酪氨酸激酶抑制剂筛选模型的建立

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浙江大学学报（农业与生命科学版） 2007年第6期33卷 646-650页

作者：汪辰卉史影龚兴国浙江大学生命科学学院生物化学研究所浙江杭州310058

在体外构建一个以src蛋白为靶位点的蛋白酪氨酸激酶抑制剂快速筛选模型,为筛选src蛋白酪氨酸激酶抑制剂奠定基础.基因工程表达GST-v-src蛋白,收集包涵体蛋白,并经变性复性处理.以生物素化的聚Glu∶Tyr(4∶1)为激酶反应底物、以辣根过氧... 详细信息

在体外构建一个以src蛋白为靶位点的蛋白酪氨酸激酶抑制剂快速筛选模型,为筛选src蛋白酪氨酸激酶抑制剂奠定基础.基因工程表达GST-v-src蛋白,收集包涵体蛋白,并经变性复性处理.以生物素化的聚Glu∶Tyr(4∶1)为激酶反应底物、以辣根过氧化物酶(horseradish peroxidase,HRP)标记的磷酸酪氨酸特异性单克隆抗体(HRP-PY20)检测磷酸酪氨酸残基的酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)测定获得蛋白的激酶活性,并进行抑制剂筛选.该模型具有靶向性强、快速、简便可行、高通量的特点.用该方法对6种治疗肿瘤配方中常用的中草药进行筛选,筛选出3种中草药水煎剂富含src蛋白酪氨酸激酶抑制剂成分.

关键词： src 蛋白酪氨酸激酶抑制剂筛选中草药

Impaired cell properties and down regulation of FAK-src complex signaling in autistic B lymphoblasts

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Impaired cell properties and down regulation of FAK-Src comp...