Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: Termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives
Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: Termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives
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DOI：
10.1006/abbi.1995.9935
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发表时间：
1995-12-01
影响因子：
3.9
通讯作者：
Freeman, BA
中科院分区：
文献类型：
--
作者：
Rubbo, H;Parthasarathy, S;Freeman, BA
脂氧合酶诱导的脂质氧化参与了血浆脂蛋白的氧化，可能是动脉粥样硬化形成的潜在致病机制。由于一氧化氮的血管松弛作用失活(.NO)在动脉粥样硬化血管功能受损中起关键作用，因为。NO与其他自由基物种快速反应，我们评估了。NO对脂氧合酶催化的亚油酸和亚麻酸的氧化、1-palmitoyl-2-arachidanyl-sn-glycero-3-phosphocholine(PC)脂质体、高胆固醇血症兔β-极低密度脂蛋白和人低密度脂蛋白的影响。大豆脂肪氧合酶(SLO)诱导的脂质氧化通过共轭双烯的积累、脂质过氧化氢的形成、耗氧量和液-质联用来评价。不同的送货率。对脂质氧化系统的否定是通过输注。没有用厌氧缓冲液或通孔平衡的气体。NO由S-亚硝基-谷胱甘肽释放。单独的一氧化氮不会导致脂质过氧化，而暴露在SLO下则会以一种金属离子不依赖的机制导致脂肪酸、脂质体或脂蛋白的显著氧化。低浓度的。NO对含铁脂肪氧合酶无明显抑制作用，但对脂质过氧化有明显的抑制作用，且呈剂量依赖关系。氧化产物的质谱分析表明生成了亚硝基、亚硝基、亚硝基过氧基和/或硝化脂氧化加合物，证明了这一点。NO是自由基链传播反应的有效终止剂。还抑制了SLO氧化亚油酸或亚麻酸与牛血清白蛋白(BSA)形成Schiff碱荧光偶合物。NO通过与脂质过氧化氢自由基(LOO)反应，从而阻止LOO的反应。带有多肽氨基。质谱分析表明，在BSA存在下，脂质过氧化产物和含氮氧化脂质物种均减少。我们得出这样的结论。NO可通过抑制脂氧合酶依赖的脂质和脂蛋白氧化，在血管壁上发挥强大的氧化保护作用。这是通过终止烷氧基(Lo.)催化的脂质自由基链传播反应实现的。还有厕所。脂质过氧化的中间体，而不是通过抑制脂氧合酶催化的启动反应。(C)1995年学术出版社。
Lipoxygenase-induced lipid oxidation contributes to plasma lipoprotein oxidation and may be an underlying pathogenic mechanism of atherogenesis. Since inactivation of the vasorelaxant actions of nitric oxide (. NO) plays a critical role in the impaired function of atherosclerotic vessels and because . NO reacts rapidly with other radical species, we assessed the influence of . NO on lipoxygenase-catalyzed oxidation of linoleic and linolenic acid, 1-palmitoyl-2-arachidanyl-sn-glycero-3-phosphocholine (PC) liposomes, hypercholesterolemic rabbit beta-very-low-density lipoprotein, and human low-density lipoprotein. Soybean lipoxygenase (SLO)-induced lipid oxidation was assessed by accumulation of conjugated dienes, formation of lipid hydroperoxides, oxygen consumption, and liquid chromatography-mass spectrometry. Different rates of delivery of . NO to lipid oxidation systems were accomplished either by infusion of . NO gas equilibrated with anaerobic buffer or via . NO released from S-nitroso-glutathione. Nitric oxide alone did not induce lipid peroxidation, while exposure to SLO yielded significant oxidation of fatty acids, PC liposomes, or lipoproteins in a metal ion-independent mechanism. Low concentrations of . NO, which did not significantly inhibit the activity of the iron-containing lipoxygenase, induced potent inhibition of lipid peroxidation in a dose-dependent manner. Mass spectral analysis of oxidation products showed formation of nitrito-, nitro-, nitrosoperoxo-, and/or nitrated lipid oxidation adducts, demonstrating that . NO serves as a potent terminator of radical chain propagation reactions. The formation of Schiffs base fluorescent conjugates between SLO-oxidized linoleic or linolenic acid and bovine serum albumin (BSA) was also inhibited by . NO via reaction with lipid hydroperoxyl radicals (LOO .), thus preventing the reaction of LOO . with polypeptide amino groups. Mass spectrometry analysis showed that both lipid peroxidation products and nitrogen-containing oxidized lipid species decreased in the presence of BSA. We conclude that . NO can play a potent oxidant-protective role in the vessel wall by inhibiting lipoxygenase-dependent lipid and lipoprotein oxidation. This occurs via termination of lipid radical chain propagation reactions catalyzed by alkoxyl (LO .) and LOO . intermediates of lipid peroxidation rather than by inhibition of lipoxygenase-catalyzed initiation reactions. (C) 1995 Academic Press, Inc.