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Two separate mechanisms are involved in membrane permeabilization during lipid oxidation

不饱和度 化学 脂质双层 膜脂 生物物理学 膜流动性 生物化学 生物膜 细胞膜 活性氧 脂质氧化 磷脂 氧化磷酸化 生物 抗氧化剂 色谱法
作者
Min Xie,Eveline H.W. Koch,Cornelis A. van Walree,Ana Sobota,Andreas F.‐P. Sonnen,Eefjan Breukink,J. Antoinette Killian,Joseph H. Lorent
出处
期刊:Biophysical Journal [Elsevier]
卷期号:122 (23): 4503-4517 被引量:1
标识
DOI:10.1016/j.bpj.2023.10.028
摘要

Lipid oxidation is a universal degradative process of cell membrane lipids that is induced by oxidative stress and reactive oxygen and nitrogen species (RONS) in multiple pathophysiological situations. It has been shown that certain oxidized lipids alter membrane properties, leading to a loss of membrane function. Alteration of membrane properties is thought to depend on the initial membrane lipid composition, such as the number of acyl chain unsaturations. However, it is unclear how oxidative damage is related to biophysical properties of membranes. We therefore set out to quantify lipid oxidation through various analytical methods and determine key biophysical membrane parameters using model membranes containing lipids with different degrees of lipid unsaturation. As source for RONS, we used cold plasma, which is currently developed as treatment for infections and cancer. Our data revealed complex lipid oxidation that can lead to two main permeabilization mechanisms. The first one appears upon direct contact of membranes with RONS and depends on the formation of truncated oxidized phospholipids. These lipids seem to be partly released from the bilayer, implying that they are likely to interact with other membranes and potentially act as signaling molecules. This mechanism is independent of lipid unsaturation, does not rely on large variations in lipid packing, and is most probably mediated via short-living RONS. The second mechanism takes over after longer incubation periods and probably depends on the continued formation of lipid oxygen adducts such as lipid hydroperoxides or ketones. This mechanism depends on lipid unsaturation and involves large variations in lipid packing. This study indicates that polyunsaturated lipids, which are present in mammalian membranes rather than in bacteria, do not sensitize membranes to instant permeabilization by RONS but could promote long-term damage.
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