FORMATION OF NON-CYCLOOXYGENASE-DERIVED PROSTANOIDS (F-2-ISOPROSTANES) IN PLASMA AND LOW-DENSITY-LIPOPROTEIN EXPOSED TO OXIDATIVE STRESS IN-VITRO
FORMATION OF NON-CYCLOOXYGENASE-DERIVED PROSTANOIDS (F-2-ISOPROSTANES) IN PLASMA AND LOW-DENSITY-LIPOPROTEIN EXPOSED TO OXIDATIVE STRESS IN-VITRO
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DOI：
10.1172/jci117107
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发表时间：
1994-03-01
影响因子：
15.9
通讯作者：
FREI, B
中科院分区：
文献类型：
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作者：
LYNCH, SM;MORROW, JD;FREI, B
F-2-异前列腺素是前列腺素F-2样化合物，已知是通过含花生四烯酰的脂质的自由基氧化在体内形成的，并且它们的血浆水平已被建议作为体内氧化应激的指标。由于 LDL 的氧化（动脉粥样硬化的可能致病因素）涉及脂质过氧化，因此我们研究了血浆中是否形成 F-2-异前列腺素，以及暴露于氧化应激的 LDL 是否形成，以及 F-2-异前列腺素的形成如何与内源性抗氧化状态相关。在暴露于水性过氧自由基的血浆中，尽管尿酸盐、α-生育酚、β-胡萝卜素和番茄红素持续存在，但内源性抗坏血酸和泛醇-10耗尽后，脂质氢过氧化物和酯化的F-2-异前列腺素同时形成。在暴露于水性过氧自由基或 Cu2+ 的分离 LDL 中，消耗内源性 ubiquinol-10 和 α-生育酚后，脂质氢过氧化物和酯化 F-2-异前列腺素快速形成并随后分解，并且 LDL 的电负性持续增加，表明发生了动脉粥样硬化修饰。在暴露于 Cu2+ 的 LDL 中，酯化 F-2-异前列烷水平的下降与游离 F-2-异前列烷的出现同时发生，表明发生了 LDL 相关活性的水解。我们的数据表明，F-2-异前列腺素是体内 LDL 氧化的有用标记。由于 F-2-异前列烷是有效的血管收缩剂，可以调节血小板聚集，因此这里证明它们在 LDL 中的形成也可能对心血管疾病的病因学具有重要意义。
F-2-isoprostanes are prostaglandin F-2-like compounds that are known to be formed in vivo by free radical oxidation of arachidonyl-containing lipids, and their plasma levels have been suggested as indicators of in vivo oxidative stress. As oxidation of LDL, a likely causal factor in atherosclerosis, involves lipid peroxidation, we investigated whether F-2-isoprostanes are formed in plasma and LDL exposed to oxidative stress, and how F-2-isoprostane formation is related to endogenous antioxidant status. In plasma exposed to aqueous peroxyl radicals, lipid hydroperoxides and esterified F-2-isoprostanes were formed simultaneously after endogenous ascorbate and ubiquinol-10 had been exhausted, despite the continued presence of urate, alpha-tocopherol, beta-carotene, and lycopene. In isolated LDL exposed to aqueous peroxyl radicals or Cu2+, consumption of endogenous ubiquinol-10 and alpha-tocopherol was followed by rapid formation and subsequent breakdown of lipid hydroperoxides and esterified F-2-isoprostanes, and a continuous increase in LDL's electronegativity, indicative of atherogenic modification. In Cu2+-exposed LDL, the decrease in esterified F-2-isoprostane levels was paralleled by the appearance of free F-2-isoprostanes, suggesting that hydrolysis by an LDL-associated activity had occurred. Our data suggest that F-2-isoprostanes are useful markers of LDL oxidation in vivo. As F-2-isoprostanes are potent vasoconstrictors and can modulate platelet aggregation, their formation in LDL demonstrated here may also have important implications for the etiology of cardiovascular disease.