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首页> 外文期刊>Biochemistry >SR-BI mediates cholesterol efflux via its interactions with lipid-bound ApoE. Structural mutations in SR-BI diminish cholesterol efflux
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SR-BI mediates cholesterol efflux via its interactions with lipid-bound ApoE. Structural mutations in SR-BI diminish cholesterol efflux

机译：SR-BI通过其与脂质结合的ApoE的相互作用介导胆固醇外流。 SR-BI中的结构突变可减少胆固醇外流

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摘要

Apolipoprotein E (apoE) and the lipoprotein receptor SR-BI play critical roles in lipid and lipoprotein metabolism. We have examined the cholesterol efflux from wild-type (WT) and mutant forms of SR-BI expressed in ldlA-7 cells using reconstituted discoidal particles consisting of apoE, 1-palmitoyl-2-oleoyl-L-phospatidylcholine (POPC), and cholesterol (C) as acceptors. POPC/C-apoE particles generated using apoE2, apoE3, apoE4, or carboxy-terminally truncated forms apoE4-165, apoE4-202, apoE4-229, and apoE4-259 caused similar (20-25%) cholesterol efflux from WT SR-131. Cholesterol efflux mediated by POPC/C-apoE was not enhanced in the presence of lipid-free apoE. The rate of cholesterol efflux mediated by particles containing the WT or carboxy-terminally truncated forms of apoE was decreased to approximately 30% of the WT control with the Q402R/Q418R mutant SR-131 form that is unable to bind native HDL normally but binds LDL. The rate of cholesterol efflux was further decreased to approximately 7% of the WT control with another SR-131 mutant (M158R) that binds neither HDL nor LDL. The level of binding of POPC/C-apoE particles (150 mu g/mL) to SR-BI mutant forms Q402R/Q418R and M158R was 70 and 8% of the WT control, respectively. SR-BI-dependent binding of lipid-free apoE to cells was undetectable, and cholesterol efflux was less than 0.5%. The findings establish that only lipid-bound apoE promotes SR-BI-mediated cholesterol efflux and that the amino-terminal region of residues 1 - 165 of apoE is sufficient for both receptor binding and cholesterol efflux. The SR-131- apoE interactions may contribute to overall cholesterol homeostasis in cells and tissues that express SR-131 and apoE.
机译：载脂蛋白E（apoE）和脂蛋白受体SR-BI在脂质和脂蛋白代谢中起关键作用。我们已经研究了ldlA-7细胞中野生型（WT）和突变形式的SR-BI的胆固醇外流，其中重组的盘状颗粒由apoE，1-棕榈酰基-2-油酰基-L-磷脂酰胆碱（POPC）和胆固醇（C）为受体。使用apoE2，apoE3，apoE4或羧基末端截短的形式apoE4-165，apoE4-202，apoE4-229和apoE4-259生成的POPC / C-apoE颗粒可导致WT SR-产生相似的（20-25％）胆固醇流出131。在无脂质的apoE的存在下，由POPC / C-apoE介导的胆固醇外流并未增强。含有WT或羧基末端截短形式的apoE的颗粒介导的胆固醇外流率降低至使用Q402R / Q418R突变SR-131形式的WT对照的约30％，后者无法正常结合天然HDL但结合LDL 。胆固醇外排率进一步降低至野生型对照的7％左右，而另一种SR-131突变体（M158R）既不结合HDL也不结合LDL。 POPC / C-apoE颗粒（150μg / mL）与SR-BI突变体Q402R / Q418R和M158R的结合水平分别为WT对照的70％和8％。 SR-BI依赖的无脂质载脂蛋白E绑定到细胞是无法检测到，并且胆固醇外流小于0.5％。这些发现证实，仅脂质结合的apoE促进SR-BI介导的胆固醇流出，并且apoE的残基1-165的氨基末端区域对于受体结合和胆固醇流出都是足够的。 SR-131-apoE相互作用可能有助于表达SR-131和apoE的细胞和组织中总体胆固醇体内平衡。

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