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首页> 外文期刊>Journal of Lipid Research >Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux.
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Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux.

机译：来自轻度氧化的低密度脂蛋白的溶酶体胆固醇对外排有抵抗力。

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In atherosclerotic lesions, macrophages store lipid in cytoplasmic inclusions and lysosomes. Regression studies show that lysosomal lipid is not as easily cleared as cytoplasmic inclusion lipid. Macrophages enriched with mildly oxidized low density lipoprotein (oxLDL) accumulate cholesteryl ester (CE) and free cholesterol (FC) in lysosomes. We examined whether lysosomal stores of cholesterol from oxLDL are cleared from THP-1 and mouse macrophages. As in previous studies, oxLDL-enriched THP-1 macrophages accumulated substantial lysosomal cholesterol. Surprisingly, less than 12% of oxLDL-derived lysosomal CE was cleared to efficient FC acceptors (e.g., cyclodextrins, apolipoprotein/phosphatidylcholine vesicles, and fetal bovine serum). Filipin staining showed that lysosomes of oxLDL-treated THP-1 cells contained FC, and despite removal of most of the cell FC (70--80%) by incubation with cyclodextrins, filipin staining of FC in lysosomes did not diminish. Also, when THP-1 macrophages were incubated with [(3)H]CE oxLDL, 73--76% of the [(3)H]CE was retained in a lysosomal hydrolysis resistant pool. In contrast, greater than 90% of acetylated low density lipoprotein (acLDL) [(3)H]CE was hydrolyzed. Furthermore, [(3)H]FC liberated from oxLDL [(3)H]CE was released at a slower rate to cyclodextrins than was [(3)H]FC from acLDL [(3)H]CE. In contrast, only 27% of oxLDL [(3)H]CE was resistant to hydrolysis in mouse macrophages, and the [(3)H]FC generated from oxLDL and acLDL [(3)H]CE was released to cyclodextrins at similar rates. We conclude that lack of hydrolysis and efflux of oxLDL cholesterol is not exclusively inherent in oxLDL, but also requires specific cell factors present in one cell type but not the other.--Yancey, P. G., and W. G. Jerome. Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux. J. Lipid Res. 2001. 42: 317--327.
机译：在动脉粥样硬化病变中，巨噬细胞将脂质存储在细胞质内含物和溶酶体中。回归研究表明，溶酶体脂质不像胞质内含脂质那样容易清除。富含轻度氧化的低密度脂蛋白（oxLDL）的巨噬细胞在溶酶体中积累胆固醇酯（CE）和游离胆固醇（FC）。我们检查了oxLDL中胆固醇的溶酶体贮藏是否从THP-1和小鼠巨噬细胞中清除。与以前的研究一样，富含oxLDL的THP-1巨噬细胞会积累大量溶酶体胆固醇。令人惊讶的是，只有不到12％的oxLDL来源的溶酶体CE被有效的FC受体（例如环糊精，载脂蛋白/磷脂酰胆碱囊泡和胎牛血清）清除。磷脂染色显示经oxLDL处理的THP-1细胞的溶酶体含有FC，尽管通过与环糊精孵育除去了大部分细胞FC（70--80％），但溶酶体中FC的菲律宾蛋白染色并没有减少。同样，当将THP-1巨噬细胞与[（3）H] CE oxLDL孵育时，[（3）H] CE的73--76％被保留在溶酶体抗水解性库中。相反，大于90％的乙酰化低密度脂蛋白（acLDL）[（3）H] CE被水解。此外，从oxLDL [[3] H] CE释放的[（3）H] FC与从acLDL [（3）H] CE的[（3）H] FC释放的速率相比，向环糊精的释放速率更慢。相反，只有27％的oxLDL [（3）H] CE抵抗小鼠巨噬细胞中的水解，并且从oxLDL和acLDL [[3] H] CE生成的[（3）H] FC在相似的情况下释放到环糊精中费率。我们得出的结论是，oxLDL胆固醇缺乏水解和外排不仅不是oxLDL固有的，而且还需要一种细胞类型中存在但不是另一种细胞类型中存在的特定细胞因子.-- Yancey，P.G.和W.G.Jerome。来自轻度氧化的低密度脂蛋白的溶酶体胆固醇对外排有抵抗力。 J.脂质研究。 2001. 42：317--327。

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