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Interaction of statins with phospholipid bilayers studied by solid-state NMR spectroscopy.
Biochim Biophys Acta Biomembr 2019; 1861(3):584-593BB

Abstract

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 1H 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.

Authors+Show Affiliations

Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russian Federation.Institute for Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, D-04107 Leipzig, Germany. Electronic address: holger.scheidt@medizin.uni-leipzig.de.Institute for Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, D-04107 Leipzig, Germany.Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russian Federation.Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russian Federation.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30578770

Citation

Galiullina, Leisan F., et al. "Interaction of Statins With Phospholipid Bilayers Studied By Solid-state NMR Spectroscopy." Biochimica Et Biophysica Acta. Biomembranes, vol. 1861, no. 3, 2019, pp. 584-593.
Galiullina LF, Scheidt HA, Huster D, et al. Interaction of statins with phospholipid bilayers studied by solid-state NMR spectroscopy. Biochim Biophys Acta Biomembr. 2019;1861(3):584-593.
Galiullina, L. F., Scheidt, H. A., Huster, D., Aganov, A., & Klochkov, V. (2019). Interaction of statins with phospholipid bilayers studied by solid-state NMR spectroscopy. Biochimica Et Biophysica Acta. Biomembranes, 1861(3), pp. 584-593. doi:10.1016/j.bbamem.2018.12.013.
Galiullina LF, et al. Interaction of Statins With Phospholipid Bilayers Studied By Solid-state NMR Spectroscopy. Biochim Biophys Acta Biomembr. 2019 03 1;1861(3):584-593. PubMed PMID: 30578770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction of statins with phospholipid bilayers studied by solid-state NMR spectroscopy. AU - Galiullina,Leisan F, AU - Scheidt,Holger A, AU - Huster,Daniel, AU - Aganov,Albert, AU - Klochkov,Vladimir, Y1 - 2018/12/20/ PY - 2018/07/20/received PY - 2018/11/23/revised PY - 2018/12/18/accepted PY - 2018/12/24/pubmed PY - 2019/11/5/medline PY - 2018/12/23/entrez KW - (1)H NMR KW - Intermolecular cross-relaxation KW - Nuclear Overhauser enhancement spectroscopy KW - Phospholipid membranes KW - Statins SP - 584 EP - 593 JF - Biochimica et biophysica acta. Biomembranes JO - Biochim Biophys Acta Biomembr VL - 1861 IS - 3 N2 - 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 1H 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. SN - 1879-2642 UR - https://www.unboundmedicine.com/medline/citation/30578770/Interaction_of_statins_with_phospholipid_bilayers_studied_by_solid-state_NMR_spectroscopy L2 - https://linkinghub.elsevier.com/retrieve/pii/S0005-2736(18)30363-8 DB - PRIME DP - Unbound Medicine ER -