Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100 secretion and triglyceride accumulation in ARPE-19 cells.
Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100 secretion and triglyceride accumulation in ARPE-19 cells.
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DOI：
10.1038/labinvest.2009.33
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发表时间：
2010-06
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影响因子：
--
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为了维持正常的视网膜功能，视网膜色素上皮（RPE）细胞吞噬富含游离脂肪酸（FFA）的光感受器外节（ROS）。我们之前已经在衰老和早期年龄相关性黄斑变性的小鼠模型中证明了 RPE/脉络膜复合体中脂肪酸结合蛋白 5 (FABP5) 的下调。 FABP 参与 FFA 的细胞内转运及其针对特定代谢途径的作用。为了阐明 FABP5 在脂质代谢中的作用，使用 RNA 干扰技术抑制人 RPE 细胞系中 FABP5 蛋白的产生。结果，经过siRNA处理后，胆固醇和胆固醇酯的水平降低了约40%，而FFA和甘油三酯的水平分别增加了18%和67%。在 siRNA 处理的细胞中，某些种类的磷脂有所减少。细胞脂滴明显，并且这些细胞中 apoB 分泌减少了 76%。此外，我们发现ARPE-19细胞可以合成和分泌载脂蛋白B100（apoB100），它可能作为这些细胞中形成脂蛋白颗粒的骨架结构。我们的结果表明，FABP5 mRNA 敲低会导致细胞甘油三酯的积累、胆固醇水平降低以及 apoB100 蛋白和脂蛋白样颗粒的分泌减少。这些观察结果表明，FABP5 在 RPE 细胞的脂质代谢中发挥着关键作用，这表明体内 RPE/脉络膜复合体中 FABP5 的下调可能会导致衰老和早期年龄相关性黄斑变性。
To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) down-regulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 down-regulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration.
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DOI：
10.1089/109793301753407948
发表时间：
2001-09-01
期刊：
IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH
影响因子：
--
作者：
McMillian, MK;Grant, ER;Johnson, MD
通讯作者：
Johnson, MD
影响因子：
6.5
作者：
Li, CM;Presley, B;Curcio, CA
通讯作者：
Curcio, CA
影响因子：
30.8
作者：
Gal, A;Li, Y;Vollrath, D
通讯作者：
Vollrath, D
影响因子：
6.5
作者：
Hertzel, AV;Bennaars-Eiden, A;Bernlohr, DA
通讯作者：
Bernlohr, DA
影响因子：
4.8
作者：
Atshaves, BP;McIntosh, AM;Schroeder, F
通讯作者：
Schroeder, F