Circulation of cholesterol between lysosomes and the plasma membrane
Circulation of cholesterol between lysosomes and the plasma membrane
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DOI：
10.1074/jbc.273.30.18915
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发表时间：
1998-07-24
影响因子：
4.8
通讯作者：
Steck, TL
中科院分区：
文献类型：
--
作者：
Lange, Y;Ye, J;Steck, TL
培养的人成纤维细胞溶酶体中的胆固醇含量约占细胞总量的6%。在Niemann-Pick型C细胞中，这个池扩大了10倍之多。某些两亲体（如U18666A、黄体酮和丙咪嗪）导致溶酶体胆固醇以类似细胞胆固醇/小时0.8%的速率升高到类似的高水平。即使在没有外源性脂蛋白的情况下，溶酶体胆固醇也会积累。此外，两种受干扰系统中几乎所有的溶酶体胆固醇都来自质膜。已知的改变胆固醇运动和体内平衡的氧甾醇阻断了两亲体处理的细胞中溶酶体胆固醇的增加，这表明这一过程是受生理调节的。用两亲体处理细胞可略微减少溶酶体的胆固醇外排，并略微增加质膜的内流，导致溶酶体胆固醇室在大约15小时内增大一倍。经过更长时间的两亲体处理后，出现了一群浮力溶酶体，它们与质膜完全但缓慢地交换胆固醇，尼曼-皮克C型溶酶体也同样浮力和迟缓。我们得出结论，胆固醇在质膜和溶酶体之间双向循环。受干扰的细胞中溶酶体胆固醇的大量积累似乎并不反映溶酶体运输障碍，而是反映为脂质储存而修饰的溶酶体的形成，即板层体。
The cholesterol in the lysosomes of cultured human fibroblasts was determined to constitute similar to 6% of the cell total. This pool was enlarged by as much as 10-fold in Niemann-Pick type C cells. Certain amphiphiles (e.g. U18666A, progesterone, and imipramine) caused lysosomal cholesterol to increase to similarly high levels at a rate of similar to 0.8% of cell cholesterol/h. Lysosomal cholesterol accumulated even in the absence of exogenous lipoproteins. Furthermore, nearly all of the lysosomal cholesterol in both of the two perturbed systems was shown to be derived from the plasma membrane. Oxysterols known to alter cholesterol movement and homeostasis blocked lysosomal cholesterol accretion in amphiphile-treated cells, suggesting that this process is regulated physiologically.Treating cells with amphiphiles slightly reduced the efflux of cholesterol from lysosomes and slightly increased the influx from the plasma membrane, causing the lysosomal cholesterol compartment to double in size in similar to 15 h. After more prolonged amphiphile treatments, a population of buoyant lysosomes appeared that exchanged cholesterol with the plasma membrane completely but slowly, Niemann-Pick type C lysosomes were similarly buoyant and sluggish.We conclude that cholesterol circulates bidirectionally between the plasma membrane and lysosomes. The massive accumulation of lysosomal cholesterol in the perturbed cells does not appear to reflect disabled lysosomal transport but rather the formation of lysosomes modified for lipid storage, i.e. lamellar bodies.