title: Effects of Phospholipase A2 Inhibitors on Bilayer Lipid Membranes.
abstract: The work examines the effect of inhibitors of cytosolic Ca(2+)-dependent and Ca(2+)-independent phospholipases A2 on bilayer lipid membranes. It was established that trifluoroperazine (TFP) and, to a lesser extent, arachidonyl trifluoromethyl ketone (AACOCF3) and palmitoyl trifluoromethyl ketone (PACOCF3) were able to permeabilize artificial lipid membranes (BLM and liposomes). It was shown that AACOCF3 lowered the temperature of phase transition of DMPC liposomes, inducing disordering of the hydrophobic region of lipid bilayer. TFP disordered membranes both in the hydrophobic region and in the region of hydrophilic heads, this being accompanied by changes in the membrane permeability: appearance of a channel-like BLM activity and leakage of sulforhodamine B from liposomes. In contrast to AACOCF3 and TFP, PACOCF3 increased membrane orderliness in the hydrophobic region (heightened the temperature of phase transition of DMPC liposomes) and in the region of lipid heads. The effectiveness of AACOCF3 and PACOCF3 as inductors of BLM and liposome permeabilization was considerably lower comparatively to TFP. As revealed by dynamic light scattering, incorporation of TFP, AACOCF3 and PACOCF3 into the membrane of liposomes resulted in the increase of the average size of particles in the suspension, presumably due to their aggregation or fusion. The paper discusses possible mechanisms of the influence of phospholipase A2 inhibitors on bilayer lipid membranes.
authors.affiliation: Mari State University, pl. Lenina 1, Yoshkar-Ola, Mari El, Russia, 424001. dubinin1989@gmail.com.|Institute of Theoretical and Experimental Biophysics RAS, Institutskaya 3, Pushchino, Moscow Region, Russia, 142290. dubinin1989@gmail.com.
authors.forename: Mikhail V
authors.identifier: 0000-0002-7453-3390
authors.initials: MV
authors.lastname: Dubinin
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, Institutskaya 3, Pushchino, Moscow Region, Russia, 142290.|Institute of Cell Biophysics RAS, Institutskaya 3, Pushchino, Moscow Region, Russia, 142290.
authors.forename: Maxim E
authors.initials: ME
authors.lastname: Astashev
authors.affiliation: Institute of Cell Biophysics RAS, Institutskaya 3, Pushchino, Moscow Region, Russia, 142290.
authors.forename: Nikita V
authors.initials: NV
authors.lastname: Penkov
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, Institutskaya 3, Pushchino, Moscow Region, Russia, 142290.|Prokhorov General Physics Institute RAS, Vavilova 38, Moscow, Russia, 119991.|Lobachevsky State University of Nizhny Novgorod, pr. Gagarina 23, Nizhny Novgorod, Russia, 603950.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Gudkov
authors.affiliation: Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, pr. Nauki 6, Pushchino, Moscow Region, Russia, 142290.|Pushchino State Institute of Natural Sciences, pr. Nauki 3, Pushchino, Moscow Region, Russia, 142290.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Dyachenko
authors.affiliation: Mari State University, pl. Lenina 1, Yoshkar-Ola, Mari El, Russia, 424001.
authors.forename: Victor N
authors.initials: VN
authors.lastname: Samartsev
authors.affiliation: Mari State University, pl. Lenina 1, Yoshkar-Ola, Mari El, Russia, 424001.|Institute of Theoretical and Experimental Biophysics RAS, Institutskaya 3, Pushchino, Moscow Region, Russia, 142290.
authors.forename: Konstantin N
authors.initials: KN
authors.lastname: Belosludtsev
mesh_terms: D002463:Cell Membrane Permeability / Q000187:drug effects; D004553:Electric Conductivity; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008561:Membrane Fusion; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D064801:Phospholipase A2 Inhibitors; D012235:Rhodamines; C022027:lissamine rhodamine B; D054467:Phospholipases A2
keywords: Lipid pores; Liposomes; Membrane fusion; Membrane permeabilization; Phase transitions; Phospholipase A2