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时间:2020-04-20
《顺铂通过p66Shc-线粒体信号通路诱导人肾小管上皮细胞凋亡.pdf》由会员上传分享,免费在线阅读,更多相关内容在应用文档-天天文库。
1、中国病理生理杂志ChineseJournalofPathophysiology2013,29(12):2167—2171·2167·[文章编号]1000—4718(2013)12—2167·05顺铂通过p66c.线粒体信号通路诱导人肾小管上皮细胞凋亡聂静,王懿春,黎祖荣,董静(湖南省肿瘤医院/中南大学湘雅医学院附属肿瘤医院ICU,湖南长沙410013)[摘要]目的:探讨O66。一线粒体信号通路在顺铂诱导的人肾小管上皮细胞凋亡中的作用。方法:体外培养人肾小管上皮细胞,Westernblotting法检测顺铂对o6
2、6及磷酸化066。(Ser36)蛋白表达的影响,然后将细胞分为对照组、顺铂组及顺铂+p66。$36A(第36位Ser突变为Ala的O66)组,用激光共聚焦显微镜观察p66。对顺铂诱导的细胞活性氧簇、线粒体活性氧簇及细胞凋亡的影响,Westernblotting法检测线粒体凋亡信号通路相关蛋白的表达。结果:顺铂促进p66蛋白磷酸化,对o66卧蛋白表达无影响;顺铂诱导细胞凋亡,细胞及线粒体活性氧簇产生增加,细胞色素c释放,caspase-9表达增加,o66。$36A可以抑制顺铂诱导的细胞氧化损伤及凋亡。结论:顺铂通
3、过p66.线粒体信号通路诱导人肾小管上皮细胞凋亡。[关键词]顺铂;线粒体;细胞凋亡;活性氧[中图分类号]R363[文献标志码]Adoi:10.3969/j.issn.1000.4718.2013.12.009Cisplatininducesapoptosisofhumanrenaltubularepithelialcellsthroughp66Shc.mitochondrialsignalpathwayNIEJing,WANGYi—chun,LIZu—rong,DONGJing(ICU,HunanProvinc
4、ialTumorHospital,TheAfiliatedTumorHospitalofXiangyaMedicalSchoolofCentralSouthUniver-sity,Changsha410013,China.E—mail:76744015@qq.corn)[ABSTRACT]AIM:ToevaluatetherolesofO66She-mitochondrialsignalpathwayinapoptosisofhumanrenaltu-bularepithelialcellsinducedbyc
5、isplatin.METHODS:Thehumanrenaltubularepithelialcellswereculturedvitro.Thelevelsofp66。andphospho-066(Ser36)proteinweredetectedbyWesternblotting.Theceilsweredividedintocon—trolgroup,cisplatingroupandcisplatin+p66“。$36A(p66。withSermutatingintoAlaatposition36)gr
6、oup.Theeffectsof066oncisplatin—inducedcellularreactiveoxygenspecies(ROS),mitochondrialROSandapoptosisweremeasuredbyconfocalmicroscopy.TheexpressionoftheproteinsrelatedtoapoptosismitoehondrialsignaltransduetionpathwaywasanalyzedbyWesternblotting.RESULTS:Cispl
7、atininducedp66phosphorylation,butdidnotafecttheexpressionofO66.CisplatinenhancedapoptosisandproductionofbothcellularandmitochondrialROS.releaseofcytochromeCandexpressionofeaspase-9.whichwereinhibitedbythetransfectionofp66$36A.CONCLUSION:Cisplatininducesapop—
8、tosisofhumanrenahubularepithelialcellsthrougho66She-mitochondrialsignalpathway.[KEYWORDS]Cisplatin;Mitochondria;Apoptosis;Reactiveoxygenspecies顺铂是一种广泛应用的抗癌药物。但由于它是细胞凋亡、炎症反应以及活性氧簇(reactiveoxygen细
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