Plasma HDL reduces nonesterified fatty acid hydroperoxides originating from oxidized LDL: a mechanism for its antioxidant ability.

Plasma HDL reduces nonesterified fatty acid hydroperoxides originating from oxidized LDL: a mechanism for its antioxidant ability.
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DOI:
10.1007/s11745-013-3779-1
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发表时间:
2013-06
期刊:
影响因子:
1.9
通讯作者:
Terao, Junji
Terao, Junji
中科院分区:
医学4区
文献类型:
--
作者:
Kotosai, Mari;Shimada, Sachiko;Kanda, Mai;Matsuda, Namiko;Sekido, Keiko;Shimizu, Yoshibumi;Tokumura, Akira;Nakamura, Toshiyuki;Murota, Kaeko;Kawai, Yoshichika;Terao, Junji

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血浆高密度脂蛋白(HDL)的抗氧化特性被认为参与了潜在的抗动脉粥样硬化作用,但确切的机制尚不清楚。我们旨在揭示高密度脂蛋白在清除氧化型低密度脂蛋白产生的过氧化脂质(LOOH)中的作用。铜离子诱导氧化制备的氧化低密度脂蛋白除含有胆固醇酯氢过氧化物(CE-OHO)和磷脂酰胆碱(PtdCHO)外,还含有非酯化脂肪酸氢过氧化物(FFA-OHO)和溶血磷脂酰胆碱(LYSOPtdCHO)。一种血小板激活因子-乙酰水解酶(PAF-AH)抑制剂可抑制氧化低密度脂蛋白中FFA-OHO和LysoPtdCho的形成。在LOOH物种中,氧化的低密度脂蛋白与高密度脂蛋白孵育优先还原FFA-OOH。高密度脂蛋白与含有FFA-OHO、CE-OHO和PtdCho-OHO的脂质体溶液混合后,表现出选择性的FFA-OHO还原能力。在高效液相分析中,13-羟基十八碳二烯酸生成了13-羟基十八碳二烯酸,证实了羟基过氧基还原为羟基。载脂蛋白A-1(apoA-1)也有这种降低作用。在氧化的低密度脂蛋白中,由于PAF-AH活性而从PtdCho-OHO中释放的FFA-OOH通过高密度脂蛋白中apoA1的还原能力进行双电子还原。这种FFA-OOH的优先降低可能参与了高密度脂蛋白抗氧化作用的机制。
The antioxidant property of plasma high-density lipoprotein (HDL) is thought to be involved in potential anti-atherogenic effects but the exact mechanism is not known. We aimed to reveal the contribution of HDL on the elimination of lipid hydroperoxides (LOOH) derived from oxidized low-density lipoprotein (LDL). Oxidized LDL prepared by copper ion-induced oxidation contained nonesterified fatty acid hydroperoxides (FFA-OOH) and lysophosphatidylcholine (lysoPtdCho), in addition to cholesteryl ester hydroperoxides (CE-OOH) and phosphatidylcholine hydroperoxides (PtdCho-OOH). A platelet-activating factor-acetylhydrolase (PAF-AH) inhibitor suppressed formation of FFA-OOH and lysoPtdCho in oxidized LDL. Among LOOH species, FFA-OOH was preferentially reduced by incubating oxidized LDL with HDL. HDL exhibited selective FFA-OOH reducing ability if it was mixed with a liposomal solution containing FFA-OOH, CE-OOH and PtdCho-OOH. Two-electron reduction of the hydroperoxy group to the hydroxy group was confirmed by the formation of 13-hydroxyoctadecadienoic acid from 13-hydroperoxyoctadecadienoic acid in HPLC analyses. This reducing effect was also found in apolipoprotein A-1 (apoA-1). FFA-OOH released from PtdCho-OOH due to PAF-AH activity in oxidized LDL undergo two-electron reduction by the reducing ability of apoA1 in HDL. This preferential reduction of FFA-OOH may participate in the mechanism of the antioxidant property of HDL.
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