Interaction of statins with phospholipid bilayers studied by solid-state NMR spectroscopy
Interaction of statins with phospholipid bilayers studied by solid-state NMR spectroscopy
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DOI：
10.1016/j.bbamem.2018.12.013
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Klochkov, Vladimir
中科院分区：
文献类型：
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作者：
Galiullina, Leisan F.;Scheidt, Holger A.;Klochkov, Vladimir
他汀类药物是特异性抑制HMG-CoA还原酶的药物，从而降低低密度脂蛋白胆固醇的浓度，低密度脂蛋白胆固醇是动脉粥样硬化发展的公认风险因素。几项临床试验的结果表明，有重要的分子间差异负责更广泛的药理作用，他汀类药物，甚至超越HMG-CoA还原酶抑制。根据一种假设，这些化合物所产生的生物效应取决于它们在细胞膜中的定位。目前工作的目的是研究不同的他汀类药物与磷脂膜的相互作用，并使用各种固态NMR技术研究其对膜结构和动力学的影响。使用H-1 NOESY MAS NMR，结果表明，阿托伐他汀，西立伐他汀，氟伐他汀，瑞舒伐他汀，和一定比例的普伐他汀插入POPC膜的脂质-水界面的程度不同。基于交叉弛豫速率，定量测定了单个他汀类药物在双层中的不同平均分布。他汀类药物对膜结构影响的研究显示，洛伐他汀对脂质堆积和链序的影响最小，普伐他汀显著降低脂质链序，而其他他汀类药物主要在磷脂链的中间段轻微降低脂质链序参数。
Statins are drugs that specifically inhibit the enzyme HMG-CoA reductase and thereby reduce the concentration of low-density lipoprotein cholesterol, which represents a well-established risk factor for the development of atherosclerosis. The results of several clinical trials have shown that there are important intermolecular differences responsible for the broader pharmacologic actions of statins, even beyond HMG-CoA reductase inhibition. According to one hypothesis, the biological effects exerted by these compounds depend on their localization in the cellular membrane. The aim of the current work was to study the interactions of different statins with phospholipid membranes and to investigate their influence on the membrane structure and dynamics using various solid-state NMR techniques. Using H-1 NOESY MAS NMR, it was shown that atorvastatin, cerivastatin, fluvastatin, rosuvastatin, and some percentage of pravastatin intercalate the lipid-water interface of POPC membranes to different degrees. Based on cross-relaxation rates, the different average distribution of the individual statins in the bilayer was determined quantitatively. Investigation of the influence of the investigated statins on membrane structure revealed that lovastatin had the least effect on lipid packing and chain order, pravastatin significantly lowered lipid chain order, while the other statins slightly decreased lipid chain order parameters mostly in the middle segments of the phospholipid chains.