Activation of autophagy in photoreceptor necroptosis after experimental retinal detachment

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    摘要 AIM:Toinvestigatewhetherphotoreceptornecroptosisinducedbyz-VAD-FMK(pancaspaseinhibitor)wasinvolvedtheactivationofautophagyandwhetherNecrostatin-1,aspecificnecroptosisinhibitor,couldinhibitthisinductionofautophagyafterexperimentalretinaldetachment.METHODS:ExperimentalretinaldetachmentmodelswerecreatedinSprague-Dawleyratsbysubretinalinjectionofsodiumhyaluronateandsubretinalinjectionsofz-VAD-FMK,vehicleorz-VAD-FMKplusNecrostatin-1.Threedaysafterretinaldetachment,morphologicchangeswereobservedbytransmissionelectronmicroscopy.Inotheranimals,retinasweresubjectedtoimmunoprecipitationandWesternBlotting,thenprobedwithanti-RIP1,phosphoserine,LC-3IIorcaspase8antibody.RESULTS:Itwasprovedbyimmunoprecipitationandwesternblotting,thatphotoreceptornecroptosiswasmediatedbycaspase-8inhibitionandreceptorinteractingproteinkinase(RIP1)phosphorylationactivation.TransmissionelectronmicroscopeandwesternblottingresultsindicatedthatphotoreceptornecroptosiswasinvolvedtheLC-3IIandautophagosomesinduction.WealsodiscoveredNecrostatin-1couldinhibitRIP1phosphorylationandLC-3IIinduction.CONCLUSION:Thesedatafirstlyindicatephotoreceptornecroptosisisassociatedwiththeactivationofautophagy.Necrostatin-1protectsphotoreceptorsfromnecroptosisandautophagybydown-regulationofRIP1phosphorylationandLC-3II.
    机构地区 不详
    出版日期 2014年05月15日(中国Betway体育网页登陆平台首次上网日期,不代表论文的发表时间)
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