Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays

Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays
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使用微阵列鉴定巨噬细胞衍生泡沫细胞形成中的脂滴相关蛋白

DOI:
10.3892/ijmm_00000457
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发表时间:
2010-08-01
影响因子:
5.4
通讯作者:
Li, Qing
Li, Qing
中科院分区:
医学3区
文献类型:
--
作者:
Li, Hang;Song, Yue;Li, Qing

文献摘要

被引文献

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大量巨噬细胞源性泡沫细胞将过量的中性脂质储存在细胞内液滴中,在动脉粥样硬化的发生发展过程中起着重要作用。脂滴相关蛋白(LD-associated proteins)是一类位于细胞内的脂滴表面的蛋白质,调节脂滴的形成、形态和脂解过程,参与细胞内脂滴的形成和分解。为了阐明LD相关蛋白在动脉粥样硬化过程中的作用,采用氧化低密度脂蛋白(ox-LDL)诱导THP-1细胞系巨噬细胞泡沫细胞模型,并利用cDNA微阵列技术检测LD相关蛋白的基因表达谱。基因表达数据显示,在泡沫细胞转化过程中,2%的变化基因是脂质结合基因。主要候选基因,细胞死亡诱导DFF 45样效应子(锡德)家族和Perilipin、Adipophilin和TIP 47(PAT)家族,在泡沫细胞形成过程中具有不同的改变。CIDEB、CIDEC、Adipophilin、S3-12和LSDP 5表达上调,而TIP 47表达下调。CIDEA和Perilipin无显著变化。这些结果通过实时PCR和免疫印迹证实。本研究对人泡沫细胞分化过程中LD相关蛋白的基因表达进行了全面的分析,这些蛋白可能在动脉粥样硬化的过程中发挥重要作用。
A large number of macrophage-derived foam cells stores excessive neutral lipids in intracellular droplets, and plays a major role during the development of atherosclerosis. The formation and catabolism of intracellular lipid droplets (LDs) are regulated by LD-associated proteins, a group of proteins which are located on the surface of LDs and regulate the formation, morphology and lipolysis of LDs. In order to illustrate the function of LD-associated proteins during the process of atherosclerosis, the foam cell model is induced by oxidized low-density lipoprotein (ox-LDL) in macrophages originated from the THP-1 cell line, and cDNA microarrays are used to monitor the gene expression profiles of LD-associated proteins. Gene expression data show that 2% of changed genes are lipid binding genes during the transformation of foam cells. The major candidate genes, the cell death-inducing DFF45-like effector (CIDE) family and Perilipin, Adipophilin, and TIP47 (PAT) family, have different alterations during the formation of foam cells. CIDEB, CIDEC, Adipophilin, S3-12 and LSDP5 were up-regulated, while TIP47 was down-regulated. There was no significant change in CIDEA and Perilipin. These results were confirmed by real-time PCR and immunoblotting. This study presents a comprehensive analysis of the gene expression of LD-associated proteins during the differentiation of human foam cells, which may play an important role in the process of atherosclerosis.