...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1
【24h】

High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1

机译：高密度脂蛋白通过ABCG1促进7-酮胆固醇的流出，从而保护巨噬细胞免受氧化的低密度脂蛋白诱导的细胞凋亡

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages and are thought to have a central role in promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown to promote efflux of cholesterol from macrophages to high-denisty lipoprotein (HDL). We show that HDL protects macrophages from apoptosis induced by loading with free cholesterol or oxidized LDL.The protective effect of HDL was reduced in Abcg1~(-/-) macrophages, especially after loading with oxidized LDL. Similarly, HDL exerted a protective effect against apoptosis induced by 7-ketocholesterol, the major oxysterol present in oxidized LDL and atherosclerotic lesions, in Abcg1~(+/+), but not in Abcg1~(-/-) macrophages. In transfected 293 cells, efflux of 7-ketocholesterol and related oxysterols was completely dependent on expression of ABCG1 and the presence of HDL in media. In contrast, ABCA1 and apoA-1 did not stimulate the efflux of 7-ketocholesterol into media. HDL stimulated the efflux of 7-ketocholesterol from Abcg1~(+/+), but not from Abcg1~(-/-) macrophages. In Abcg1~(-/-) mice fed a high-cholesterol diet, plasma levels of 7-ketocholesterol were reduced, whereas their macrophages accumulated 7-ketocholesterol. These findings indicate a specific role for ABCG1 in promoting efflux of 7-ketocholesterol and related oxysterols from macrophages onto HDL and in protecting these cells from oxysterol-induced cytotoxicity.
机译：饮食中消耗的或在低密度脂蛋白（LDL）上形成的氧化固醇对内皮细胞和巨噬细胞有毒，并被认为在促进动脉粥样硬化中起核心作用。最近显示，ATP结合盒转运蛋白ABCG1可以促进胆固醇从巨噬细胞向高密度脂蛋白（HDL）的流出。我们发现HDL保护巨噬细胞免于负载游离胆固醇或氧化的LDL诱导的凋亡.HDL对Abcg1〜（-/-）巨噬细胞的保护作用降低，尤其是负载氧化LDL后。类似地，HDL在Abcg1〜（+ / +）中对氧化的LDL和动脉粥样硬化病变中存在的主要氧固醇7-酮胆固醇具有保护作用，而在Abcg1〜（-/-）巨噬细胞中则没有。在转染的293细胞中，7-酮胆固醇和相关氧固醇的外排完全取决于ABCG1的表达和HDL在培养基中的存在。相反，ABCA1和apoA-1不会刺激7-酮胆固醇排入培养基。 HDL刺激Abcg1〜（+ / +）流出7-酮胆固醇，而不刺激Abcg1〜（-/-）巨噬细胞流出。在饲喂高胆固醇饮食的Abcg1〜（-/-）小鼠中，血浆7-酮胆固醇水平降低，而它们的巨噬细胞则积累了7-酮胆固醇。这些发现表明ABCG1在促进7-酮胆固醇和相关的氧固醇从巨噬细胞向HDL的外排以及在保护这些细胞免受氧固醇诱导的细胞毒性中起特定作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号