The Journal of Membrane Biology

, Volume 249, Issue 3, pp 339–347 | Cite as

Effects of Phospholipase A2 Inhibitors on Bilayer Lipid Membranes

  • Mikhail V. DubininEmail author
  • Maxim E. Astashev
  • Nikita V. Penkov
  • Sergey V. Gudkov
  • Igor A. Dyachenko
  • Victor N. Samartsev
  • Konstantin N. Belosludtsev


The work examines the effect of inhibitors of cytosolic Ca2+-dependent and Ca2+-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.


Phospholipase A2 Liposomes Membrane permeabilization Membrane fusion Lipid pores Phase transitions 



Phospholipase A2


Arachidonyl trifluoromethyl ketone


Palmitoyl trifluoromethyl ketone




Bilayer lipid membrane


Large unilamellar vesicles




Sulforhodamine B


Dynamic light scattering


Generalized polarization


Differential scanning calorimetry


Triton X-100



The work was supported by the grants from the Russian Foundation for Basic Research to K.N. Belosludtsev (15-34-50346, 15-04-03081-a) and to V.N. Samartsev (14-04-00688-a) by the Government of Russian Federation (Project No. 14.Z50.31.0028) and by the Ministry for Education and Science of Russian Federation to V.N. Samartsev (State Order no. 1365).


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mikhail V. Dubinin
    • 1
    • 2
    Email author
  • Maxim E. Astashev
    • 2
    • 3
  • Nikita V. Penkov
    • 3
  • Sergey V. Gudkov
    • 2
    • 4
    • 5
  • Igor A. Dyachenko
    • 6
    • 7
  • Victor N. Samartsev
    • 1
  • Konstantin N. Belosludtsev
    • 1
    • 2
  1. 1.Mari State UniversityYoshkar-OlaRussia
  2. 2.Institute of Theoretical and Experimental Biophysics RASPushchinoRussia
  3. 3.Institute of Cell Biophysics RASPushchinoRussia
  4. 4.Prokhorov General Physics Institute RASMoscowRussia
  5. 5.Lobachevsky State University of Nizhny NovgorodNizhny NovgorodRussia
  6. 6.Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RASPushchinoRussia
  7. 7.Pushchino State Institute of Natural SciencesPushchinoRussia

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