...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Cholesterol Mobilization by Free and Lipid-Bound ApoAI_Milano and ApoAI_Milano-ApOAII Heterodimers
【24h】

Cholesterol Mobilization by Free and Lipid-Bound ApoAI_Milano and ApoAI_Milano-ApOAII Heterodimers

机译：游离和脂质结合的ApoAI_Milano和ApoAI_Milano-ApOAII异二聚体对胆固醇的动员

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

Despite very low plasma levels of HDL, carriers of the apolipoprotein AI Arg173 -Cys mutation apoAIMilano (AIM) have no apparent increase in risk for atherosclerotic vascular disease. HDL apolipoprotein species in AIM carriers include apoAI-AII heterodimers, previously found to confer the enhanced ability of tyrosyl radical-oxidized HDL to mobilize cholesterol for removal from cultured cells. To determine whether enhanced mobilization of cholesterol by apoprotein species in AIM explains a cardioprotective action of this mutation, we examined the ability of lipid-free and lipid-bound AIM and AIM-AII heterodimers to deplete cholesterol from cultured cells. Free AIM and AIM-AII heterodimers showed a decreased capacity to act as acceptors of cholesterol from cholesterol-loaded human fibroblasts compared with native apoAI but similar capacities to deplete fibroblasts of the pool of cholesterol available for esterification by acyl-CoA:cholesterol acyltransferase (ACAT). Discoidal reconstituted HDL (rHDL) containing apoAI depleted both of these cholesterol pools more readily than AIM-containing rHDL when compared at equivalent rHDL protein levels, but similar abilities of these rHDL to deplete cell cholesterol were seen when compared at equivalent phospholipid levels. Spherical rHDL generated using the whole lipid fraction of HDL and apoAI or AIM showed similar capacities to deplete total and ACA T -accessible cell cholesterol when compared at similar protein levels, but an increased capacity of AIM-containing particles was seen when compared at equivalent phospholipid levels. Unlike the apoAI-AII heterodimer in tyrosylated HDL, AIM-AII heterodimer-containing spherical rHDL showed no increased capacity to deplete either of these pools of cholesterol. These results suggest a similar or better capacity of native apoAI in lipid-free or lipid-bound form in discoidal rHDL to enhance the mobilization of cellular cholesterol when compared to AIM in its free or lipid-bound forms. Any increase in depletion of cellular cholesterol by lipid-bound AIM in spherical rHDL appears related to altered phospholipid-binding rather than intrinsic cholesterol-mobilizing characteristics of this protein compared to native apoAI. The lack of major differences in these studies in cholesterol mobilization by native apoAI and AIM, or by apoAIM-AII heterodimers, suggests that any protection against atherosclerosis conferred by this mutation is likely related to other beneficial vascular effects of AIM
机译：尽管血浆中的HDL水平非常低，但载脂蛋白AI Arg173-Cys突变apoAIMilano（AIM）的携带者的动脉粥样硬化性血管疾病风险没有明显增加。 AIM携带者中的HDL载脂蛋白种类包括apoAI-AII异二聚体，以前发现它们具有增强的酪氨酰自由基氧化HDL调动胆固醇从培养细胞中去除的能力。为了确定AIM中载脂蛋白物质对胆固醇的增强动员是否解释了这种突变的心脏保护作用，我们研究了无脂质和脂质结合的AIM和AIM-AII异二聚体消耗培养细胞中胆固醇的能力。与天然apoAI相比，游离的AIM和AIM-AII异二聚体显示出从载有胆固醇的人成纤维细胞中充当胆固醇受体的能力降低，但在可用于酰基辅酶A：胆固醇酰基转移酶（ACAT）酯化作用的胆固醇库中，耗尽胆固醇的成纤维细胞的能力相似）。在等效的rHDL蛋白水平下，含apoAI的盘状重构HDL（rHDL）比包含AIM的rHDL更容易消耗这两个胆固醇，但是在相同的磷脂水平下，这些rHDL消耗细胞胆固醇的能力相似。当以相似的蛋白质水平进行比较时，使用HDL的全部脂质级分和apoAI或AIM生成的球形rHDL表现出相似的能力来消耗总胆固醇和ACA T可及的细胞胆固醇，但是当与同等的磷脂相比时，包含AIM的颗粒的能力却有所提高水平。与酪氨酰化HDL中的apoAI-AII异源二聚体不同，含AIM-AII异源二聚体的球形rHDL并未显示出消耗这些胆固醇中任何一个的增加的能力。这些结果表明，与游离或脂质结合形式的AIM相比，盘状rHDL中无脂质或脂质结合形式的天然apoAI具有相似或更好的能力来增强细胞胆固醇的动员。与天然apoAI相比，球形rHDL中通过脂质结合的AIM引起的细胞胆固醇消耗的任何增加似乎都与该蛋白的磷脂结合改变而非固有的胆固醇动员特性有关。在这些研究中，天然apoAI和AIM或apoAIM-AII异二聚体在胆固醇动员方面缺乏主要差异，这表明这种突变所赋予的对动脉粥样硬化的任何保护都可能与AIM的其他有益血管作用有关

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