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典型文献
ox-LDL induces autophagy-mediated apoptosis by suppressing secretagogin-regulated autophagic flux in pancreatic β-cells
文献摘要:
Lipotoxicity has been shown to induce the loss of functional β-cell mass and lead to type 2 diabetes,but the mechanism remains unknown.In this study,we aim to explore the role of secretagogin(SCGN)in lipotoxicity-induced β-cell injury.Our results indicate that ox-LDL treatment leads to autophagic cell death,as evidenced by decreased cell viability,aggravated cell apoptosis,and the accumulation of the p62 protein in MIN6 cells.Lyso-Tracker Red staining,TEM and mRFP-GFP-LC3 assays demonstrate that autophagic flux is blocked in ox-LDL-treated MING cells.Intriguingly,SCGN is significantly decreased in MIN6 cells under lipotoxic conditions.Additionally,siRNA-guided SCGN knockdown blocks autophagic flux triggered by rapamycin,while SCGN restoration alleviates autophagic flux retardation and mitigates cell apoptosis.The physical interaction between SCGN and SNAP29 is validated by bioinformatics analysis,coimmunoprecipitation assay and SCGN knockdown test.Downregulation of SCGN expression reduces the interaction of these two proteins.Taken together,our results indicate that ox-LDL treatment induces apoptotic β-cell death by blocking autophagic flux dependent on SCGN downregulation.SCGN administration prevents lipotoxic β-cell injury and may be a potential therapeutic strategy to promote β-cell ex-pansion in type 2 diabetes.
文献关键词:
作者姓名:
Ying Lv;Sijie Xiao;Shuhui Ouyang;Zhengliang Peng;Li Wu;Ziqing Tang;Weizheng Zhang;Renxian Cao;Jing Yang
作者机构:
The First Affiliated Hospital,Department of Clinical Research,Hengyang Medical School,University of South China,Hengyang 421001,China;The Second Affiliated Hospital,Department of Metabolism and Endocrinology,Hengyang Medical School,University of South China,Hengyang 421001,China;The First Affiliated Hospital,Department of Metabolism and Endocrinology,Hengyang Medical School,University of South China,Hengyang 421001,China;The First Affiliated Hospital,Department of Emergency,Hengyang Medical School,University of South China,Hengyang 421001,China
引用格式:
[1]Ying Lv;Sijie Xiao;Shuhui Ouyang;Zhengliang Peng;Li Wu;Ziqing Tang;Weizheng Zhang;Renxian Cao;Jing Yang-.ox-LDL induces autophagy-mediated apoptosis by suppressing secretagogin-regulated autophagic flux in pancreatic β-cells)[J].生物化学与生物物理学报(英文版),2022(12):1822-1831
A类:
secretagogin,Lipotoxicity,lipotoxicity,MING,lipotoxic
B类:
LDL,induces,autophagy,mediated,apoptosis,by,suppressing,regulated,autophagic,flux,pancreatic,cells,has,been,shown,loss,functional,mass,type,diabetes,but,mechanism,remains,unknown,this,study,aim,explore,role,SCGN,induced,injury,Our,results,indicate,that,treatment,leads,death,evidenced,decreased,viability,aggravated,accumulation,p62,MIN6,Lyso,Tracker,Red,staining,TEM,mRFP,GFP,LC3,assays,demonstrate,blocked,treated,Intriguingly,significantly,under,conditions,Additionally,siRNA,guided,knockdown,blocks,triggered,rapamycin,while,restoration,alleviates,retardation,mitigates,physical,interaction,between,SNAP29,validated,bioinformatics,analysis,coimmunoprecipitation,test,Downregulation,expression,reduces,these,two,proteins,Taken,together,our,apoptotic,blocking,dependent,downregulation,administration,prevents,may,potential,therapeutic,strategy,promote,pansion
AB值:
0.526173
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