侧链氧化氧甾醇在人体循环中的运输

Amir Babiker , Ulf Diczfalusy
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引用次数: 133

摘要

为了研究24-羟基胆固醇、27-羟基胆固醇和3β-羟基-5-胆固醇酸在循环中的转运,测定了这些氧甾醇在血浆、极低密度脂蛋白、低密度脂蛋白、高密度脂蛋白和无脂蛋白血浆中的分布。采用同位素稀释-质谱法,采用单个氘标记内标。24-羟基胆固醇和27-羟基胆固醇主要与HDL和LDL相关,而3β-羟基-5-胆固醇酸主要存在于无脂蛋白部分。24-羟基胆固醇和27-羟基胆固醇在血浆中主要以酯化形式存在,而3β-羟基-5-胆固醇酸仅以游离酸形式存在。为了便于比较,在血浆和分离的脂蛋白中测定了许多其他的氧甾醇。在血浆分离过程中,胆固醇自氧化形成了大量的这些氧甾醇。因此,不可能计算出这些氧甾醇在不同血浆组分中的分布。目前的结果与我们之前的发现一致,即极性较低的胆固醇代谢物27-羟基胆固醇与胆固醇竞争,以HDL作为受体分子运输出细胞,而极性较强的化合物3β-羟基-5-胆固醇酸的运输则由白蛋白促进。
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Transport of side-chain oxidized oxysterols in the human circulation

To study the transport of 24-hydroxycholesterol, 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid in the circulation, the distribution of these oxysterols was determined in plasma, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and lipoprotein-free plasma. An accurate method based on isotope dilution-mass spectrometry with use of individual deuterium labeled internal standards was used. 24-Hydroxycholesterol and 27-hydroxycholesterol were found to be associated mainly with HDL and LDL, whereas 3β-hydroxy-5-cholestenoic acid was found predominantly in the lipoprotein-free fraction. While both 24-hydroxycholesterol and 27-hydroxycholesterol are present mainly in esterified form in plasma, 3β-hydroxy-5-cholestenoic acid was present as free acid only. For reasons of comparison, a number of other oxysterols were determined in plasma and in isolated lipoprotein fractions. Significant amounts of these oxysterols were formed by cholesterol autoxidation during fractionation of plasma. It was therefore not possible to calculate the distribution of these oxysterols in the different plasma fractions. The present results are consistent with our previous finding that the less polar cholesterol metabolite 27-hydroxycholesterol competes with cholesterol for transport out of cells using HDL as an acceptor molecule, whereas the transport of the more polar compound 3β-hydroxy-5-cholestenoic acid is facilitated by albumin.

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