ADRP/adipophilin is degraded through the proteasome-dependent pathway during regression of lipid-storing cells
ADRP/adipophilin is degraded through the proteasome-dependent pathway during regression of lipid-storing cells
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DOI：
10.1194/jlr.m500170-jlr200
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发表时间：
2006-01-01
影响因子：
6.5
通讯作者：
Takano, T
中科院分区：
文献类型：
--
作者：
Masuda, Y;Itabe, H;Takano, T
脂肪分化相关蛋白（ADRP）是巨噬细胞源性泡沫细胞和肝细胞等多种细胞中与脂滴相关的主要蛋白质。然而，ADRP在这些细胞的形成和消退过程中的作用尚不清楚。当J774小鼠巨噬细胞与VLDL或油酸孵育时，其ADRP和三酰甘油（TG）的含量增加3至4倍。在油酸处理的HuH-7人肝细胞中也观察到TG积累期间ADRP的诱导。添加三酸甘油酯C，一种有效的酰基辅酶A合成酶抑制剂，6小时降低TG的量在VLDL诱导的泡沫细胞和油酸处理的肝细胞，它减少了ADRP蛋白的量平行，表明ADRP的量减少在消退的脂质储存细胞。在triacsin C处理期间添加蛋白酶体抑制剂消除了ADRP降低和聚泛素化ADRP积累。此外，该蛋白酶体抑制剂不仅逆转了三酸甘油酯C对ADRP的降解，而且逆转了三酸甘油酯C对TG的降低。这些结果表明，ADRP和TG的细胞量相互调节，泛素-蛋白酶体系统参与ADRP的降解过程中的脂质储存细胞的退化。
Adipose differentiation-related protein (ADRP) is a major protein associated with lipid droplets in various types of cells, including macrophage-derived foam cells and liver cells. However, the role of ADRP in the processes of formation and regression of these cells is not understood. When J774 murine macrophages were incubated with either VLDL or oleic acid, their content of both ADRP and triacylglycerol (TG) increased 3- to 4-fold. Induction of ADRP during TG accumulation was also observed in oleic acid-treated HuH-7 human liver cells. Addition of triacsin C, a potent inhibitor of acyl-CoA synthase, for 6 h decreased the amount of TG in VLDL-induced foam cells and oleic acid-treated liver cells; it decreased the amount of ADRP protein in parallel, indicating the amount of ADRP reduced during regression of the lipid-storing cells. Addition of a proteasome inhibitor during triacsin C treatment abolished the ADRP decrease and accumulated polyubiquitinated ADRP. In addition, the proteasome inhibitor reversed not only the degradation of ADRP but also TG reduction by triacsin C. These results suggest that cellular amounts of ADRP and TG regulate each other and that the ubiquitin-proteasome system is involved in degradation of ADRP during regression of lipid-storing cells.