Cell death-inducing DFF45-like effector b (Cideb) is present in pancreatic beta-cells and involved in palmitate induced beta-cell apoptosis
Cell death-inducing DFF45-like effector b (Cideb) is present in pancreatic beta-cells and involved in palmitate induced beta-cell apoptosis
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诱导细胞死亡的 DFF45 样效应器 b (Cideb) 存在于胰腺 β 细胞中，并参与棕榈酸酯诱导的 β 细胞凋亡
DOI：
10.1002/dmrr.1295
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发表时间：
2012-02-01
影响因子：
8
通讯作者：
Li, Q.
中科院分区：
文献类型：
--
作者：
Li, H.;Song, Y.;Li, Q.
背景：胰岛中长链脂肪酸的过度积聚与胰岛β细胞功能障碍有关，并最终导致2型糖尿病的发病。已有研究证明，细胞死亡诱导的DFF45样效应子b(Cideb)参与细胞凋亡和脂质代谢。方法采用逆转录-聚合酶链式反应、免疫组织化学和免疫印迹等方法，观察Cideb在胰腺组织和克隆性β细胞系中的表达。在游离脂肪酸(FFA)和Cideb核糖核酸干扰下检测Cideb的生理作用，并通过末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷缺口末端标记法和caspase-3活性进一步分析细胞凋亡。尼罗红染色和甘油三酯定量检测脂质蓄积。结果Cideb在胰腺中大量表达，主要定位于胰岛β细胞。游离脂肪酸，尤其是棕榈酸酯，可明显增加β细胞系中CideB的表达。正常情况下，腺病毒介导的Cideb过表达增加了β-TC3细胞的凋亡率，而基于核糖核酸干扰的Cideb缺失对细胞的凋亡没有影响。补充棕榈酸酯可导致胰岛β细胞脂凋亡，而Cideb沉默加剧了棕榈酸酯诱导的β细胞凋亡，降低了细胞内甘油三酯的含量，加重了β细胞的FFA超载。结论棕榈酸暴露时Cideb表达增加可能通过影响脂滴中游离脂肪酸向脂酯的转化而参与β细胞脂肪细胞的凋亡。版权所有(C)2011 John Wiley&Sons，Ltd.
Background Excessive accumulation of long-chain fatty acids in the pancreatic islets is associated with beta cell dysfunction and ultimately contributes to the pathogenesis of type 2 diabetes. It has been well proved that the cell death-inducing DFF45-like effector b (Cideb) is involved in cell apoptosis and lipid metabolism. However, the expression and function of Cideb in endocrine pancreas remain to be investigated.Methods By using reverse transcript polymerase chain reaction, immunohistochemistry and Western blot, we observed the expression of Cideb in pancreas tissues and clonal beta-cell lines. The physiological role of Cideb was examined under the free fatty acid (FFA) administration and Cideb ribonucleic acid interference, and further analysis on apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay and caspase-3 activity. Nile red staining and quantitative evaluation of triglyceride were used to detect the lipid accumulation. The changes in esterification of FFA were traced by radiolabelled palmitate.Results Cideb was abundantly expressed in pancreas and mainly localized in beta cells. FFAs, especially palmitate, induced an obvious increase of Cideb expression in beta cell lines. Adenoviral-mediated overexpression of Cideb increased the apoptosis, whereas ribonucleic acid interference-based Cideb depletion in beta-TC3 cells had no effect on apoptosis in normal condition. Palmitate supplementation led to beta cell lipoapoptosis, and Cideb silencing exacerbated the apoptosis induced by palmitate, reduced intracellular triglyceride content and aggravated FFA overload in beta cells.Conclusions The present results suggest that increased Cideb expression upon palmitate exposure may be involved in beta cell lipoapoptosis through its influence on conversion of FFAs to lipid esters in lipid droplets. Copyright (C) 2011 John Wiley & Sons, Ltd.