NDRG2 is highly expressed in pancreatic β cells and involved in protection against lipotoxicity

被引：0
作者：
Lan Shen
Xuewu Liu
Wugang Hou
Guodong Yang
Yousheng Wu
Rui Zhang
Xia Li
Honglei Che
Zifan Lu
Yuanqiang Zhang
Xinping Liu
Libo Yao
机构：
[1] The Fourth Military Medical University,Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology
[2] The Fourth Military Medical University,Department of Histology and Embryology
[3] Xijing Hospital,Department of Anesthesiology
[4] The Fourth Military Medical University,undefined
来源：
Cellular and Molecular Life Sciences | 2010年 / 67卷
关键词：
NDRG2; Pancreatic β cell; Protein kinase Akt; Free fatty acid; Apoptosis;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The N-myc downstream-regulated gene 2 (NDRG2) is involved in cell differentiation and apoptosis, but its function in the pancreas remains to be established. Herein we examine the expression and function of NDRG2 in the endocrine pancreas. NDRG2 immunoreactivity was localized mainly in the cytoplasm of pancreatic β cells. When β-TC3 cells were exposed chronically to high levels of free fatty acid (FFA), cell viability was impaired, and Akt and NDRG2 phosphorylation were reduced. NDRG2 is a potential substrate of protein kinase Akt. Overexpression of constitutively active Akt enhanced NDRG2 phosphorylation and abolished the apoptosis induced by FFA in β-TC3 cells, whereas NDRG2 knock-down attenuated Akt-mediated protection of β cells against fatty acid-triggered apoptosis. Collectively, these data indicate that NDRG2 acts as a key molecule in pancreatic β cells and is involved in the Akt-mediated protection of β cells against lipotoxicity.
引用
收藏
页码：1371 / 1381
页数：10
相关论文
共 278 条
[21]  
Wang YZ(2006)ErbB2 degradation mediated by the co-chaperone protein CHIP J Biol Chem 281 21942-21953
[22]  
Ji SP(2000)Free fatty acid inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase Eur J Biochem 267 5421-5426
[23]  
Liu XW(2005)The neuronal Ca Diabetes 54 968-975
[24]  
Che HL(2005) sensor protein visinin-like protein-1 is expressed in pancreatic islets and regulates insulin secretion J Cell Sci 118 3905-3915
[25]  
Lin W(2004)Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity Endocrinology 145 5087-5096
[26]  
Li X(2007)Endoplasmic reticulum stress-induced apoptosis is partly mediated by reduced insulin signaling through phosphatidylinositol 3-kinase/Akt and increased glycogen synthase kinase-3β in mouse insulinoma cells Diabetologia 50 752-763
[27]  
Zhang J(2008)ER stress and SREBP-1 activation are implicated in β-cell glucolipotoxicity Acta Biochim Biophys Sin 40 625-635
[28]  
Yao LB(2008)Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-κB and endoplasmic reticulum stress Cell Physiol Biochem 21 239-250
[29]  
Deng Y(2008)Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes Nucleic Acids Res 36 5335-5349
[30]  
Yao L(2002)NDRG2: a Myc-repressed gene involved in cancer and cell stress Endocrinology 143 339-342
12345678910