Hydrodioxyl (perhydroxyl), peroxyl, and hydroxyl radical-initiated lipid peroxidation of large unilamellar vesicles (liposomes): comparative and mechanistic studies.
Hydrodioxyl (perhydroxyl), peroxyl, and hydroxyl radical-initiated lipid peroxidation of large unilamellar vesicles (liposomes): comparative and mechanistic studies.
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氢二氧基（过羟基）、过氧化氢和羟基自由基引发的大单层囊泡（脂质体）的脂质过氧化：比较和机制研究。
DOI：
10.1006/abbi.1993.1455
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发表时间：
1993
影响因子：
3.9
通讯作者：
Dix,TA
中科院分区：
文献类型：
--
作者：
Aikens,J;Dix,TA
以生物膜结构模型大单膜囊泡（LUV）脂质体为氧化靶点，研究了生物氧化o2衍生氧化剂引发脂质过氧化的机制和相对效率。当由含有0或5 mol%过氧化氢（LOOH）的二烯油基磷脂酰胆碱（DLPC）制备LUVs时，以亚油酸或DLPC过氧化氢的形式加入，保持了结构的完整性，从而可以评估氧化剂在双分子层外生成时引发脂质过氧化的相对能力。luv比分散在溶液中的多层囊泡或脂质更容易氧化，支持其作为生物膜模型的适用性。与先前使用脂质分散剂的结果平行(J. Aikens and T. A. Dix, 1991，J。医学杂志。化学，266,15091-15098)，过羟基（HOO.）和过氧（ROO.）自由基在LUVs中引发脂质过氧化。不引发的氧化剂包括H2O2，有机氢过氧化物，最明显的是超氧化物（O−2）。呼!。ROO。由不同的机制发起：HOO。需要预先存在的looh的存在才能有效启动，这表明HOO的直接反应。loh，而ROO。由脂肪酸侧链上不饱和双烯基位置的氢原子抽离引起。与ROO相比，羟基自由基（HO.s）是较差的引发剂。(还有，间接地，HOO。S)，这可能会被认为是令人惊讶的，因为后者是化学上较弱的氧化剂。HO活性降低。并不是因为接触luv的机会减少；相反，这种氧化剂似乎反应产生不太可行的脂质过氧化繁殖物种。实验还表明，LUV膜的流动性对各氧化剂的相对引发活性影响不大。有人认为，HO。在体内只能间接引发脂质过氧化（通过产生碳基过氧自由基，ROO）。(5)，并应更努力了解HOO的角色。ROO。脂质过氧化起始。
The mechanisms and relative efficiencies of lipid peroxidation initiation by biological O2-derived oxidants were studied using large unilammellar vesicle (LUV) liposomes, structural models for biological membranes, as targets for oxidation. LUVs, when prepared from dilinoleoylphosphatidylcholine (DLPC) containing either 0 or 5 mol% hydroperoxide (LOOH, added either as a linoleic acid or DLPC hydroperoxide), maintained structural integrity, which enabled evaluation of the relative ability of oxidants to initiate lipid peroxidation when generated outside of the bilayer. LUVs were more oxidizable than multilamellar vesicles or lipids dispersed in solution, supporting their appropriateness as biological membrane models. In parallel to previous results using lipid dispersions (J. Aikens and T. A. Dix, 1991,J. Biol. Chem.266, 15091-15098), both perhydroxyl (HOO.) and peroxyl (ROO.) radicals initiated lipid peroxidation in LUVs. Oxidants that did not initiate included H2O2, organic hydroperoxides, and, most notably, superoxide (O−2). HOO.and ROO.initiated by different mechanisms: HOO.required the presence of the preexisting LOOHs for efficient initiation, indicating the direct reaction of HOO.with LOOH, whereas ROO.initiated by hydrogen atom abstraction at the bisallylic site of unsaturation on the fatty acid side chain of the PCs. Hydroxyl radicals (HO.s) were poor initiators in comparison to ROO.s (and, indirectly, HOO.s), which might be considered surprising as the latter species are chemically weaker oxidants. The decreased activity of HO.was not due to decreased access to the LUVs; rather, this oxidant appears to react to generate less viable lipid peroxidation propagating species. It was also demonstrated that the fluidity of the LUV membrane had little effect on the relative initiating activity of each oxidant. It is argued that HO.may initiate lipid peroxidation only indirectlyin vivo(through the generation of carbon-based peroxyl radicals, ROO.s) and that greater effort should be made to understand the roles of HOO.and ROO.at lipid peroxidation initiation.