NDRG2 在胰腺β细胞中高度表达，参与对抗脂毒性的保护作用。
NDRG2 is highly expressed in pancreatic beta cells and involved in protection against lipotoxicity.
机构信息
Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, China.
出版信息
Cell Mol Life Sci. 2010 Apr;67(8):1371-81. doi: 10.1007/s00018-010-0258-1. Epub 2010 Feb 3.
Abstract
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 beta cells. When beta-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 beta-TC3 cells, whereas NDRG2 knock-down attenuated Akt-mediated protection of beta cells against fatty acid-triggered apoptosis. Collectively, these data indicate that NDRG2 acts as a key molecule in pancreatic beta cells and is involved in the Akt-mediated protection of beta cells against lipotoxicity.
摘要
N-霉酰基天冬氨酸下游调节基因 2（NDRG2）参与细胞分化和细胞凋亡，但它在胰腺中的功能尚待确定。在此，我们研究了 NDRG2 在胰岛中的表达和功能。NDRG2 免疫反应主要定位于胰岛β细胞的细胞质中。当β-TC3 细胞长期暴露于高水平游离脂肪酸（FFA）时，细胞活力受损，Akt 和 NDRG2 磷酸化减少。NDRG2 是蛋白激酶 Akt 的潜在底物。组成型激活 Akt 的过表达增强了 NDRG2 的磷酸化，并消除了 FFA 在β-TC3 细胞中诱导的细胞凋亡，而 NDRG2 的敲低则减弱了 Akt 介导的对β细胞的脂肪酸诱导的细胞凋亡的保护作用。总之，这些数据表明，NDRG2 作为胰腺β细胞中的关键分子，参与了 Akt 介导的对β细胞的脂毒性的保护作用。
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3
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