Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch
Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch
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氧化脂质在 H2O2 通过脂质膜渗透中的作用：抑制剂到启动子开关的分子机制
DOI：
10.1038/s41598-019-48954-z
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发表时间：
2019
影响因子：
4.6
通讯作者：
Nabika Hideki
中科院分区：
文献类型：
--
作者：
Ouchi Yuya;Unoura Kei;Nabika Hideki
H2 O2渗透通过细胞膜显着影响生物体，渗透是由脂质和其他膜成分的物理化学性质控制。我们使用三种氧化脂质研究了H2 O2渗透与脂质膜结构之间的分子关系。POVPC和PazePC分别充当分子内和分子间渗透促进剂;然而，它们的潜在机制不同。前者改变了分配平衡，而后者改变了渗透途径。在我们的实验条件下，PoxnoPC通过分子内构型变化抑制渗透。因此，内和分子间的过程被发现控制氧化脂质的作用，作为抑制剂和促进剂对H2 O2渗透与不同的机制，取决于结构和组成。在这里，我们确定了两个独立的H2 O2渗透途径：（i）渗透通过脂质膜与增加分配系数的分子内构型变化和（ii）扩散通过孔（水通道）形成的氧化脂质的分子间构型变化。我们提供了新的见解，生物细胞如何控制渗透的分子通过内和分子间的脂质膜的构型变化。因此，通过对氧化脂质和其他组分进行合理设计，可以控制H2 O2和其他离子和分子通过脂质膜的渗透行为。
H2O2permeation through a cell membrane significantly affects living organisms, and permeation is controlled by the physico-chemical nature of lipids and other membrane components. We investigated the molecular relationship between H2O2permeation and lipid membrane structure using three oxidized lipids. POVPC and PazePC act as intra- and inter-molecular permeation promoters, respectively; however, their underlying mechanisms were different. The former changed the partition equilibrium, while the latter changed the permeation pathway. PoxnoPC inhibited permeation under our experimental conditions via an intra-molecular configuration change. Thus, both intra- and inter-molecular processes were found to control the role of oxidized lipids as inhibitors and promoters towards H2O2permeation with different mechanisms depending on structure and composition. Here, we identified two independent H2O2permeation routes: (i) permeation through lipid membrane with increased partition coefficient by intra-molecular configurational change and (ii) diffusion through pores (water channels) formed by inter-molecular configurational change of oxidized lipids. We provide new insight into how biological cells control permeation of molecules through intra- and inter-molecular configurational changes in the lipid membrane. Thus, by employing a rational design for both oxidized lipids and other components, the permeation behaviour of H2O2and other ions and molecules through a lipid membrane could be controlled.