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Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic beta-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways
Hao, Feng; Kang, Jinsen; Cao, Yajun; Fan, Shengjun; Yang, Haopeng; An, Yu; Pan, Yan; Tie, Lu; Li, Xuejun
关键词Curcumin Palmitate Lipotoxicity Apoptosis beta-Cells FoxO1
刊名APOPTOSIS
2015-11-01
DOI10.1007/s10495-015-1150-0
20期:11页:1420-1432
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]ENDOPLASMIC-RETICULUM STRESS ; FREE FATTY-ACIDS ; STIMULATED INSULIN-RELEASE ; OXIDATIVE STRESS ; DIABETIC-RATS ; HIGH GLUCOSE ; ER STRESS ; PROTEIN ; ISLETS ; LIPOTOXICITY
英文摘要

Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic beta-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in beta-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic beta-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic beta-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.

语种英语
WOS记录号WOS:000361817200002
项目编号81473235 ; 91129727 ; 81020108031 ; 81270049 ; 81373405 ; 30901803 ; B07001 ; YETP0053 ; BMU20110254 ; JRCC2011
资助机构National Natural Science Foundation of China ; Ministry of Education of China (111 Projects) ; Beijing Higher Education Young Elite Teacher Project ; Leading Academic Discipline Project of Beijing Education Bureau ; Fund of Janssen Research Council China
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59390
专题北京大学基础医学院
北京大学医学部管理机构_医学部
作者单位Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol,Beijing Key Lab Tumor Syst Biol,St, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Hao, Feng,Kang, Jinsen,Cao, Yajun,et al. Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic beta-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways[J]. APOPTOSIS,2015,20(11):1420-1432.
APA Hao, Feng.,Kang, Jinsen.,Cao, Yajun.,Fan, Shengjun.,Yang, Haopeng.,...&Li, Xuejun.(2015).Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic beta-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways.APOPTOSIS,20(11),1420-1432.
MLA Hao, Feng,et al."Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic beta-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways".APOPTOSIS 20.11(2015):1420-1432.
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