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首页> 美国卫生研究院文献>The Journal of Clinical Investigation >Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.
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Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.

机译：模仿载脂蛋白A-1的合成两亲性螺旋肽可清除细胞胆固醇。

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Clearance of excess cholesterol from cells by HDL is facilitated by the interaction of HDL apolipoproteins with cell-surface binding sites or receptors, a process that may be important in preventing atherosclerosis. In this study, synthetic peptides containing 18-mer amphipathic helices of the class found in HDL apolipoproteins (class A) were tested for their abilities to remove cholesterol and phospholipid from cultured sterol-laden fibroblasts and macrophages and to interact with cell-surface HDL binding sites. Lipid-free peptides containing two identical tandem repeats of class A amphipathic helices promoted cholesterol and phospholipid efflux from cells and depleted cellular cholesterol accessible for esterification by acyl CoA/cholesterol acyltransferase, similar to what was observed for purified apolipoprotein A-I. Peptide-mediated removal of plasma membrane cholesterol and depletion of acyl CoA/cholesterol acyltransferase-accessible cholesterol appeared to occur by separate mechanisms, as the latter process was less dependent on extracellular phospholipid. The dimeric amphipathic helical peptides also competed for high-affinity HDL binding sites on cholesterol-loaded fibroblasts and displayed saturable high-affinity binding to the cell surface. In contrast, peptides with a single helix had little or no ability to remove cellular cholesterol and phospholipid, or to interact with HDL binding sites, suggesting that cooperativity between two or more helical repeats is required for these activities. Thus, synthetic peptides comprising dimers of a structural motif common to exchangeable apolipoproteins can mimic apolipoprotein A-I in both binding to putative cell-surface receptors and clearing cholesterol from cells.
机译：高密度脂蛋白载脂蛋白与细胞表面结合位点或受体的相互作用促进了高密度脂蛋白清除细胞中多余的胆固醇，这一过程在预防动脉粥样硬化中可能很重要。在这项研究中，测试了包含在HDL载脂蛋白（A类）中发现的18-mer两亲性螺旋的合成肽的能力，这些肽能够从培养的固醇成纤维细胞和巨噬细胞中去除胆固醇和磷脂，并与细胞表面HDL结合相互作用网站。含有两个相同的A类两亲性螺旋串联重复序列的无脂质肽促进了胆固醇和磷脂从细胞的排出，并耗尽了可通过酰基CoA /胆固醇酰基转移酶酯化的细胞胆固醇，这与纯化载脂蛋白A-I观察到的相似。肽介导的质膜胆固醇的去除和酰基辅酶A /胆固醇酰基转移酶可及的胆固醇的消耗似乎是通过单独的机制发生的，因为后者的过程较少依赖于细胞外磷脂。二聚体两亲性螺旋肽还竞争装载胆固醇的成纤维细胞上的高亲和力HDL结合位点，并表现出可饱和的高亲和力结合至细胞表面。相反，具有单个螺旋的肽几乎没有或没有去除细胞胆固醇和磷脂或与HDL结合位点相互作用的能力，这表明这些活性需要两个或多个螺旋重复序列之间的协同作用。因此，包含与可交换载脂蛋白共同的结构基序二聚体的合成肽可以模拟载脂蛋白A-1与假定的细胞表面受体结合并从细胞清除胆固醇。

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