State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, P.R. China.
Int J Mol Med. 2010 Aug;26(2):231-9. doi: 10.3892/ijmm_00000457.
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.
大量的巨噬细胞源性泡沫细胞在细胞内液滴中储存过多的中性脂质,在动脉粥样硬化的发展过程中起主要作用。细胞内脂滴 (LDs) 的形成和分解代谢受 LD 相关蛋白调节,这些蛋白位于 LDs 的表面,调节 LDs 的形成、形态和脂解。为了说明 LD 相关蛋白在动脉粥样硬化过程中的作用,用氧化型低密度脂蛋白 (ox-LDL) 诱导源自 THP-1 细胞系的巨噬细胞中的泡沫细胞模型,并使用 cDNA 微阵列监测 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 DFF45 样效应物 (CIDE) 家族和 Perilipin、Adipophilin、和 TIP47 (PAT) 家族在泡沫细胞形成过程中有不同的改变。CIDEB、CIDEC、Adipophilin、S3-12 和 LSDP5 上调,而 TIP47 下调。CIDEA 和 Perilipin 没有明显变化。这些结果通过实时 PCR 和免疫印迹得到证实。本研究全面分析了人泡沫细胞分化过程中 LD 相关蛋白的基因表达,这可能在动脉粥样硬化过程中起重要作用。