NADPH Oxidase 2-Derived Reactive Oxygen Species Mediate FFAs-Induced   Dysfunction and Apoptosis of beta-Cells via JNK, p38 MAPK and p53   Pathways

doi:10.1371/journal.pone.0015726

CORC > 北京大学 > 工学院

	NADPH Oxidase 2-Derived Reactive Oxygen Species Mediate FFAs-Induced Dysfunction and Apoptosis of beta-Cells via JNK, p38 MAPK and p53 Pathways
	Yuan, Huiping ; Zhang, Xiaoyong ; Huang, Xiuqing ; Lu, Yonggang ; Tang, Weiqing ; Man, Yong ; Wang, Shu ; Xi, Jianzhong ; Li, Jian
刊名	plos one
	2010
关键词	INDUCED INSULIN-SECRETION HUMAN PANCREATIC-ISLETS LONG-TERM EXPOSURE FREE FATTY-ACIDS ENDOPLASMIC-RETICULUM STRESS TRANSCRIPTION FACTOR PDX-1 OXIDATIVE STRESS GENE-EXPRESSION DIABETES-MELLITUS RAT ISLETS
DOI	10.1371/journal.pone.0015726
英文摘要	Dysfunction of beta-cell is one of major characteristics in the pathogenesis of type 2 diabetes. The combination of obesity and type 2 diabetes, characterized as 'diabesity', is associated with elevated plasma free fatty acids (FFAs). Oxidative stress has been implicated in the pathogenesis of FFA-induced beta-cell dysfunction. However, molecular mechanisms linking between reactive oxygen species (ROS) and FFA-induced beta-cell dysfunction and apoptosis are less clear. In the present study, we test the hypothesis that NOX2-derived ROS may play a critical role in dysfunction and apoptosis of beta-cells induced by FFA. Our results show that palmitate and oleate (0.5 mmol/L, 48 h) induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells. We also found that palmitate and oleate stimulated apoptosis of NIT-1 cells through p38MAPK, p53 and NF-kappa B pathway. More interestingly, our data suggest that suppression of NOX2 may restore FFA-induced dysfunction and apoptosis of NIT-1 cells. Our findings provide a new insight of the NOX2 as a potential new therapeutic target for preservation of beta-cell mass and function.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000285793200043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Multidisciplinary Sciences; SCI(E); PubMed; 42; ARTICLE; 12; e15726; 5
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/315702]
专题	工学院
推荐引用方式 GB/T 7714	Yuan, Huiping,Zhang, Xiaoyong,Huang, Xiuqing,et al. NADPH Oxidase 2-Derived Reactive Oxygen Species Mediate FFAs-Induced Dysfunction and Apoptosis of beta-Cells via JNK, p38 MAPK and p53 Pathways[J]. plos one,2010.
APA	Yuan, Huiping.,Zhang, Xiaoyong.,Huang, Xiuqing.,Lu, Yonggang.,Tang, Weiqing.,...&Li, Jian.(2010).NADPH Oxidase 2-Derived Reactive Oxygen Species Mediate FFAs-Induced Dysfunction and Apoptosis of beta-Cells via JNK, p38 MAPK and p53 Pathways.plos one.
MLA	Yuan, Huiping,et al."NADPH Oxidase 2-Derived Reactive Oxygen Species Mediate FFAs-Induced Dysfunction and Apoptosis of beta-Cells via JNK, p38 MAPK and p53 Pathways".plos one (2010).