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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dual roles for cholesterol in mammalian cells.
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Dual roles for cholesterol in mammalian cells.

机译：胆固醇在哺乳动物细胞中的双重作用。

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摘要

The structural features of sterols required to support mammalian cell growth have not been fully defined. Here, we use mutant CHO cells that synthesize only small amounts of cholesterol to test the capacity of various sterols to support growth. Sterols with minor modifications of the side chain (e.g., campesterol, beta-sitosterol, and desmosterol) supported long-term growth of mutant cells, but sterols with more complex modifications of the side chain, the sterol nucleus, or the 3-hydroxy group did not. After 60 days in culture, the exogenous sterol comprised >90% of cellular sterols. Inactivation of residual endogenous synthesis with the squalene epoxidase inhibitor NB-598 prevented growth in beta-sitosterol and greatly reduced growth in campesterol. Growth of cells cultured in beta-sitosterol and NB-598 was restored by adding small amounts of cholesterol to the medium. Surprisingly, enantiomeric cholesterol also supported cell growth, even in the presence of NB-598. Thus, sterols fulfill two roles inmammalian cells: (i) a bulk membrane requirement in which phytosterols can substitute for cholesterol and (ii) other processes that specifically require small amounts of cholesterol but are not enantioselective.
机译：支持哺乳动物细胞生长所需的固醇的结构特征尚未完全确定。在这里，我们使用仅合成少量胆固醇的突变CHO细胞来测试各种固醇支持生长的能力。对侧链进行了微小修饰的甾醇（例如，菜油甾醇，β-谷甾醇和去氢甾醇）可支持突变细胞的长期生长，但对侧链，固醇核或3-羟基具有更复杂修饰的固醇没有。培养60天后，外源固醇占细胞固醇的＞ 90％。用角鲨烯环氧酶抑制剂NB-598使残留的内源性合成失活可阻止β-谷甾醇的生长，并大大降低菜油甾醇的生长。通过在培养基中添加少量胆固醇，可以恢复在β-谷甾醇和NB-598中培养的细胞的生长。出乎意料的是，即使存在NB-598，对映体胆固醇也支持细胞生长。因此，固醇在哺乳动物细胞中扮演两个角色：（i）大量膜的需求，其中植物固醇可以代替胆固醇；（ii）其他需要少量胆固醇但不对映选择性的过程。

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