Oxidative susceptibility of low density lipoprotein subfractions is related to their ubiquinol-10 and alpha-tocopherol content.

Oxidative susceptibility of low density lipoprotein subfractions is related to their ubiquinol-10 and alpha-tocopherol content.
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DOI:
10.1073/pnas.91.3.1183
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发表时间:
1994-02
影响因子:
11.1
通讯作者:
D. Tribble;J. V. D. van den Berg;P. Motchnik;B. Ames;D. Lewis;A. Chait;R. Krauss
D. Tribble;J. V. D. van den Berg;P. Motchnik;B. Ames;D. Lewis;A. Chait;R. Krauss
中科院分区:
综合性期刊1区
文献类型:
--
作者:
D. Tribble;J. V. D. van den Berg;P. Motchnik;B. Ames;D. Lewis;A. Chait;R. Krauss

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共轭多烯脂肪酸Parinaric acid(PNA)在氧化时会经历化学计量的荧光损失,可用于直接监测脂质环境中的过氧化应激。我们通过监测PNA掺入高密度脂蛋白(p=1.026-1.032 g/ml)和高密度脂蛋白(p=1.040-1.054 g/ml)低密度脂蛋白亚组分中的氧化程度,评估了低密度脂蛋白潜在致动脉粥样硬化氧化变化的过程。铜诱导的低密度脂蛋白相关PNA的氧化表现出最初的滞后阶段,随后损失速度增加,直到耗尽。在食用抗氧化剂泛喹酚-10和α-生育酚之后,但在共轭双烯显著升高之前,PNA的氧化增加立即发生。尽管对早期氧化事件的敏感性不同,但PNA氧化和共轭二烯滞后时间是相关的(r=0.582;P=0.03),两者都表明与先前的报告一致,密度低密度脂蛋白比浮力低密度脂蛋白更容易发生。在密度较高的低密度脂蛋白中,PNA的敏感性更高,这归因于泛喹酚-10和α-生育酚水平的降低,这两种物质比浮力低密度脂蛋白(抗氧化剂摩尔/低密度脂蛋白摩尔)低约50%,共同解释了PNA氧化滞后时间变化的80%。这些结果表明,PNA是一个有用的低密度脂蛋白氧化敏感性的探针,在监测低密度脂蛋白脂质过氧化的早期阶段可能优于共轭双烯类化合物。低密度脂蛋白密度亚组分之间氧化敏感性的差异是通过PNA分析检测到的,这在很大程度上是由于它们的抗氧化剂含量的差异。
The conjugated polyene fatty acid parinaric acid (PnA) undergoes a stoichiometric loss in fluorescence upon oxidation and can be used to directly monitor peroxidative stress within lipid environments. We evaluated the course of potentially atherogenic oxidative changes in low density lipoproteins (LDL) by monitoring the oxidation of PnA following its incorporation into buoyant (p = 1.026-1.032 g/ml) and dense (p = 1.040-1.054 g/ml) LDL subfractions. Copper-induced oxidation of LDL-associated PnA exhibited an initial lag phase followed by an increased rate of loss until depletion. Increased PnA oxidation occurred immediately after the antioxidants ubiquinol-10 and alpha-tocopherol were consumed but before there were marked elevations in conjugated dienes. Despite differences in sensitivity to early oxidation events, PnA oxidation and conjugated diene lag times were correlated (r = 0.582; P = 0.03), and both indicated a greater susceptibility of dense than buoyant LDL in accordance with previous reports. The greater susceptibility of PnA in dense LDL was attributed to reduced levels of ubiquinol-10 and alpha-tocopherol, which were approximately 50% lower than in buoyant LDL (mol of antioxidant/mol of LDL) and together accounted for 80% of the variation in PnA oxidation lag times. These results suggest that PnA is a useful probe of LDL oxidative susceptibility and may be superior to conjugated dienes for monitoring the initial stages of LDL lipid peroxidation. Differences in oxidative susceptibility among LDL density subfractions are detected by the PnA assay and are due in large part to differences in their antioxidant content.