简介:ObjectivesToinvestigatetheassociationofsolubleFasligand(sFasL)andsolubleFasreceptor(sFas)withhumanchroniccongestiveheartfailure(CHF).MethodsTheserumlevelofsFasLandsFasin33patientswithCHF(13incardiacfunctionclassⅡ,17inclassⅢ,3inclassⅣ,NYHA)wasassessedwithenzyme-linkedimmunosorbentassay,andwascomparedwiththatof18age-,bloodpressure-matchedpatientswithcardiacfunctionclassⅠ(NYHA).ResultsTherewasnodifferenceinthelevelofsFasLbetweenthetwogroups[CHFgroup:231.50+/-84.50(cardiacfunctionclassⅡ216.50+/-96.00,classⅢ226.80+/-85.70,classⅣ244.00+/-73.00)vs.cardiacfunctionclassIgroup:217.50+/-89.00pg/mL,P>0.05].However,thelevelofsFaswassignificantlyhigherinthepatientswithCHFthanthoseofcardiacfunctionclassIgroup[CHFgroup:1353.30+/-507.71(cardiacfunctionclassⅡ1154.85+/-371.20,classⅢ1412.88+/-493.62,classⅣ1875.67+/-806.
简介:<正>Fasligand(FasL)wasfirstdescribedfunctionallyasaninduciblecellsurfacemoleculeusedbycytotoxicTcellstoinduceapoptoticcelldeathintumorcellsandactivatedlymphocytes.WiththeidentificationofFasastheIprgeneproduct,FasLbecamerecognizedasamoleculeinvolvedindown-regulationoftheimmunesystem.WhileFasLcanbeusedtoefficientlykillFas-expressingtumorcellsaswellasactivatedTandBlymphocytesinvitro,attemptstouseFasLtherapeuticallytotreatcancerortopreventtransplant
简介:摘要目的对糖尿病性白内障及老年性白内障晶状体上皮细胞(LEC)的凋亡及其与上皮细胞Fas、P53基因的相关性进行分析探讨。方法本次研究对象选取我院2012年1月至2016年12月收治的48例行超乳手术的老年白内障患者,获取患者中央部的晶状体前囊膜。并按照其是否合并糖尿病将其分为A组(糖尿病性老年白内障组,n=24)与B组(非糖尿病性老年白内障组,n=24),应用光镜、电镜等方法观察LEC的凋亡情况,并以RT-PCR定量检测Fas、P53基因在白内障晶状体上皮细胞中的表达情况。结果光镜下显示A组患者的白内障上皮细胞呈透明眼,可见空泡,凋亡细胞较B组明显增多。电镜下显示A组患者的白内障上皮细胞可见凋亡小体,而B组中未见凋亡小体,且就凋亡情况来讲,A组较B组明显增多。两组患者的上皮细胞中均存在Fas、P53基因的表达,且Fas在糖尿病性白内障上皮细胞中的平均表达为老年白内障的12.32倍,P53蛋白在糖尿病性白内障上皮细胞中的平均表达为老年白内障的7.22倍,差异比较具有统计学意义(P<0.05)。结论老年白内障患者晶体上皮细胞中P53与Fas存在表达,提示着P53与Fas基因参与晶体上皮细胞凋亡的整体调控,对于治疗眼科疾病的外源性抑癌基因,其表达水平的监测具有重要意义。
简介:目的探讨黄芪对实验性病毒性心肌炎细胞凋亡及Fas/FasL基因的影响.方法Balb/c小鼠24只腹腔感染柯萨奇病毒B3(CVB3)后随机分成2组:治疗组(每天腹腔注射黄芪注射液100mg/10g)及对照组.第8d取心脏标本,进行病理学检查、细胞凋亡TUNEL法检测以及逆转录聚合酶链反应(RT-PCR)分析Fas和FasLmRNA的表达水平.结果①黄芪治疗组病变积分明显低于对照组(P<0.01).②黄芪治疗组心肌细胞凋亡指数(AI)明显低于对照组(P<0.01).③黄芪治疗组心肌组织Fas和FasL的mRNA相对表达量均明显低于对照组(P<0.01,P<0.05).结论黄芪可通过下调病毒性心肌炎小鼠心肌组织Fas和FasL基因转录,减少心肌细胞凋亡和心肌损伤.
简介:摘要目的观察亚砷酸钠(NaAsO2)对人正常肝细胞(L-02细胞)脂代谢基因固醇调节元件结合蛋白-1c(SREBP-1c)、过氧化物酶体增殖物激活受体α(PPARα)和脂肪酸合成酶(FAS)表达的影响。方法体外培养L-02细胞,分别以0(对照)、2、4、8、16、32、64、128 μmol/L NaAsO2染砷24 h,采用CCK-8法检测细胞存活率,并制作拟合曲线计算半抑制浓度(IC50),以IC50的0、1/8、1/4、1/2作为染砷剂量进行后续实验。采用甘油磷酸氧化酶-过氧化氢酶(GPO-PAP)法检测细胞甘油三酯(TG)含量;实时荧光定量PCR检测SREBP-1c、PPARα、FAS mRNA表达水平;蛋白质印迹法(Western blot)检测SREBP-1c和PPARα蛋白表达水平。结果8、16、32、64、128 μmol/L NaAsO2组细胞存活率[(92.000 ± 1.414)%、(91.000 ± 0.000)%、(76.500 ± 0.707)%、(53.000 ± 1.412)%、(47.000 ± 1.412)%]明显低于对照组[(100.000 ± 0.000)%,P均< 0.01],IC50为64 μmol/L,以0(对照)、8、16、32 μmol/L NaAsO2进行后续实验。与对照组[(1.000 ± 0.000)mmol/g prot]比较,8、16、32 μmol/L NaAsO2组TG含量[(0.691 ± 0.064)、(0.474 ± 0.162)、(0.184 ± 0.045)mmol/g prot]显著降低(P均< 0.01)。与对照组比较,各染砷组SREBP-1c、PPARα、FAS mRNA表达水平,SREBP-1c、PPARα蛋白表达水平显著降低(P < 0.01或< 0.05)。相关性分析可见,NaAsO2含量与细胞TG含量,SREBP-1c和PPARα蛋白表达水平呈负相关(r =-0.954、- 0.875、- 0.965,P均< 0.01)。结论NaAsO2可引起L-02细胞TG含量减少及脂代谢相关基因SREBP-1c、PPARα和FAS表达降低,提示砷致肝损伤过程中可引起脂代谢障碍发生。
简介:ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.
简介:<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson
简介:摘要目的研究FAS-670A/G基因多态与吉非替尼治疗敏感性及患者生存之间的关系。方法入组88例接受吉非替尼单药治疗的IIIA-IV期非小细胞肺癌患者,分析FAS-670A/G基因多态与吉非替尼治疗的临床获益率及患者生存的相关性。结果FAS-670A/G基因多态与全组患者临床获益率无关。AA、AG、GG患者的2年总生存率分别为49.2%、49.2%和28.7%,有显著差异(P=0.028);携带A等位基因的患者,2年总生存率高于GG基因型患者,分别为49.3%和28.7%,有统计学意义(P=0.007)。多因素预后分析显示病理类型(P=0.020,RR2.466,95%CI1.150-5.288)和FAS-670多态性(P=0.036,RR0.503,95%CI0.264-0.955)是独立的预后因素。结论促进肿瘤细胞凋亡是吉非替尼抗肿瘤作用的重要部分,FAS-670A/G基因多态可能成为吉非替尼治疗的进展期非小细胞肺癌患者生存的预测指标。
简介:IncreasedexpressionofFasbyhematopoieticprogenitorsinaplasticanemia(AA)suggeststhatFas/Fasligand(FasL)systemplaysakeyroleintheformationofseverepancytopenia.Tofurtherconfirmtheabovehypothesis,Tcellsfrom8patientswithAAweresystematicallystudiedfortheirFasL'sdistributionpattern,releasingmannerandproapoptoticactivity,comparedwithnormalrestingTcellsandartificiallyactivatedTcellblasts.TheresultsdemonstratedthatAATcellsabnormallyexpressedlowlevelsofmembrane-boundFasLandcontainedhighlevelsofintracellularFasLwhichcouldbetriggeredtoreleasebyhigh-dosephytohemagglutinin(PHA)pulse-stimulation.ThesupernatantsfromthePHA-stimulatedAATcellshadapparentcytotoxicityagainstFasL-sensitiveJurkatcells,whichcouldbesignificantlyinhibitedbymonoclonalantibodyagainstFasLinadose-dependentmanner,ornearlycompletelyabrogatedbyultracentrifugation.TheabovephenomenaalsoappearedonartificiallyactivatedTcellblasts,butthiswasnotthecaseonnormalrestingTcells.TheseresultsindicatethatAATcellisatypeof'preactivated'Tlymphocyte,characterizedbyoverexpressionofFasL,especiallyintracellularFasLwhichcanbestimulatedtoreleaseinbioavtiveexosomesboundform.Takentogether,ourdataprovidefurtheranddirectevidenceforthehypothesisthatTcellsmightmediatethedestructionofhematopieticprogenitorinAAthroughFas/FasLsystem.