Recycling of vitamin E in human low density lipoproteins.
Recycling of vitamin E in human low density lipoproteins.
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发表时间：
1992-03
影响因子：
6.5
通讯作者：
V. Kagan;E. Serbinova;T. Forte;G. Scita;L. Packer
中科院分区：
文献类型：
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作者：
V. Kagan;E. Serbinova;T. Forte;G. Scita;L. Packer
低密度脂蛋白（LDL）的氧化修饰及其不受限制的清道夫受体依赖性摄取被认为是巨噬细胞源性泡沫细胞中胆固醇沉积的原因。已经表明，由LDL转运的维生素E在保护LDL免受氧化方面起着关键作用。我们假设LDL中维持足够高的维生素E浓度可以通过减少其色满氧基自由基来实现，即，维生素E的回收利用在这项研究中，我们证明：i）内源性维生素E和外源性添加的α-生育三烯酚、α-生育酚或其具有6-碳侧链的合成同系物色原烷醇-α-C6的色原烷氧基自由基可以通过紫外（UV）光或通过与酶氧化系统产生的过氧自由基相互作用在人LDL中直接产生（脂氧合酶+亚麻酸）或通过偶氮引发剂，2，2 '-偶氮-双（2，4-二甲基戊腈）（AMVN）ii）抗坏血酸可通过直接还原LDL中的色烷氧基自由基来回收内源性维生素E和外源性添加的色烷醇; iii）二氢硫辛酸不能有效地直接还原色满氧基自由基，但通过与抗坏血酸盐协同相互作用而分解维生素E（减少脱氢抗坏血酸盐，从而保持抗坏血酸盐的稳态浓度）;和iv）β-胡萝卜素在维生素E再循环中没有活性，但其本身可以被保护免受色满氧基自由基的还原剂的氧化破坏。我们认为血浆还原剂对维生素E和其他酚类抗氧化剂的再循环可能是LDL增强抗氧化保护的重要机制。
Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptor-dependent uptake is believed to account for cholesterol deposition in macrophage-derived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be achieved by reducing its chromanoxyl radicals, i.e., by vitamin E recycling. In this study we demonstrate that: i) chromanoxyl radicals of endogenous vitamin E and of exogenously added alpha-tocotrienol, alpha-tocopherol or its synthetic homologue with a 6-carbon side-chain, chromanol-alpha-C6, can be directly generated in human LDL by ultraviolet (UV) light, or by interaction with peroxyl radicals produced either by an enzymic oxidation system (lipoxygenase + linolenic acid) or by an azo-initiator, 2,2'-azo-bis(2,4-dimethylvaleronitrile) (AMVN; ii) ascorbate can recycle endogenous vitamin E and exogenously added chromanols by direct reduction of chromanoxyl radicals in LDL; iii) dihydrolipoic acid is not efficient in direct reduction of chromanoxyl radicals but recycles vitamin E by synergistically interacting with ascorbate (reduces dehydroascorbate thus maintaining the steady-state concentration of ascorbate); and iv) beta-carotene is not active in vitamin E recycling but may itself be protected against oxidative destruction by the reductants of chromanoxyl radicals. We suggest that the recycling of vitamin E and other phenolic antioxidants by plasma reductants may be an important mechanism for the enhanced antioxidant protection of LDL.