期刊
BIOCHEMISTRY AND BIOPHYSICS REPORTS
卷 28, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbrep.2021.101143
关键词
Statin; Model membrane; POPC bilayer; MAS NMR; Order parameters
资金
- German Academic Exchange Service DAAD
- German research foundation DFG [SCHE 1755/4-1]
- Kazan Federal University [0671-2020-0051, 0671-20200058]
Pitavastatin, a statin drug, can lower cholesterol levels by affecting membrane structure, but its lipophilicity leads to localization in cellular membranes, potentially causing changes in membrane structure.
Pitavastatin is a statin drug that, by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can lower serum cholesterol levels of low-density lipoprotein (LDL) accompanied by side effects due to pleiotropic effects leading to statin intolerance. These effects can be explained by the lipophilicity of statins, which creates membrane affinity and causes statin localization in cellular membranes. In the current report, the interaction of pitavastatin with POPC model membranes and its influence on the membrane structure were investigated using H-1, H-2 and P-31 solid-state NMR spectroscopy. Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the P-31 NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.
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