Effect of Modified Levopimaric Acid Diene Adducts on Mitochondrial and Liposome Membranes

被引：4

作者：

Dubinin, Mikhail, V ^{[1
]}

Sharapov, Vyacheslav A. ^{[1
]}

Semenova, Alena A. ^{[1
]}

Parfenova, Lyudmila, V ^{[2
]}

Ilzorkina, Anna I. ^{[3
]}

Khoroshavina, Ekaterina, I ^{[1
]}

Belosludtseva, Natalia, V ^{[3
]}

Gudkov, Sergey, V ^{[4
]}

Belosludtsev, Konstantin N. ^{[1
,3
]}

机构：

[1] Mari State Univ, Dept Biochem Cell Biol & Microbiol, Pl Lenina 1, Yoshkar Ola 424001, Russia

[2] Russian Acad Sci, Ufa Fed Res Ctr, Inst Petrochem & Catalysis, Prospekt Oktyabrya 141, Ufa 450075, Russia

[3] Russian Acad Sci, Inst Theoret & Expt Biophys, Inst Skaya 3, Pushchino 142290, Russia

[4] Russian Acad Sci, Prokhorov Gen Phys Inst, Vavilov St 38, Moscow 119991, Russia

来源：

MEMBRANES | 2022年 / 12卷 / 09期

基金：

俄罗斯基础研究基金会;

关键词：

levopimaric acid diene adducts; mitochondria; oxidative phosphorylation; ROS; liposomes; membrane permeability; ABIETANE DITERPENOID LIBRARY; DERIVATIVES; IDENTIFICATION; LAURDAN; BETULIN; PROTEIN; ROS;

D O I：

10.3390/membranes12090866

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This paper demonstrates the membranotropic effect of modified levopimaric acid diene adducts on liver mitochondria and lecithin liposomes. We found that the derivatives dose-dependently reduced the efficiency of oxidative phosphorylation of mitochondria due to inhibition of the activity of complexes III and IV of the respiratory chain and protonophore action. This was accompanied by a decrease in the membrane potential in the case of organelle energization both by glutamate/malate (complex I substrates) and succinate (complex II substrate). Compounds 1 and 2 reduced the generation of H2O2 by mitochondria, while compound 3 exhibited a pronounced antioxidant effect on glutamate/malate-driven respiration and, on the other hand, caused ROS overproduction when organelles are energized with succinate. All tested compounds exhibited surface-active properties, reducing the fluidity of mitochondrial membranes and contributing to nonspecific permeabilization of the lipid bilayer of mitochondrial membranes and swelling of the organelles. Modified levopimaric acid diene adducts also induced nonspecific permeabilization of unilamellar lecithin liposomes, which confirmed their membranotropic properties. We discuss the mechanisms of action of the tested compounds on the mitochondrial OXPHOS system and the state of the lipid bilayer of membranes, as well as the prospects for the use of new modified levopimaric acid diene adducts in medicine.

引用

页数：15