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学科主题: 基础医学
题名:
Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic beta-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways
作者: 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
发表日期: 2015-11-01
DOI: 10.1007/s10495-015-1150-0
卷: 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
所属项目编号: 81473235 ; 91129727 ; 81020108031 ; 81270049 ; 81373405 ; 30901803 ; B07001 ; YETP0053 ; BMU20110254 ; JRCC2011
项目资助者: 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
WOS记录号: WOS:000361817200002
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59390
Appears in Collections:基础医学院_期刊论文

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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

Recommended Citation:
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.
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