Belosludtsev 2018 Biochemistry (Mosc)

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Belosludtsev KN, Belosludtseva NV, Tenkov KS, Sharapov VA, Kosareva EA, Dubinin MV (2018) Effect of dequalinium on respiration and the inner membrane permeability of rat liver mitochondria. Biochemistry (Mosc) 12:121–27.

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Belosludtsev KN, Belosludtseva NV, Tenkov KS, Sharapov VA, Kosareva EA, Dubinin MV (2018) Biochemistry (Mosc)

Abstract: The effect of the lipophilic penetrating cation dequalinium on rat liver mitochondria was studied. It was found that dequalinium dose-dependently inhibits the respiration rate of rat liver mitochondria in ADP-stimulated (V3) and DNP-stimulated (uncoupled) states. This can be due to the fact that dequalinium is a potent inhibitor of complex III of the mitochondrial respiratory chain. It was shown that dequalinium induces a high-amplitude swelling of rat liver mitochondria. The dequalinium-induced swelling of the organelles depends on the presence of inorganic phosphate in the incubation medium: in the absence of phosphate or in the presence of the phosphate carrier inhibitor mersalyl in the phosphate-containing medium, no swelling of the mitochondria was observed. At low concentrations of dequalinium (≤10 μM), this swelling is inhibited by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. At the same time, at high concentrations of dequalinium (>10 μM), cyclosporin A becomes ineffective. It was found that in the presence of dequalinium the rate of the H2O2 production increased in rat liver mitochondria. Possible mechanisms of toxic effect of dequalinium chloride are discussed.

Keywords: Dequalinium, Mitochondria, Oxidative phosphorylation, Respiratory chain complexes, Mitochondrial permeability transition pore Bioblast editor: Plangger M

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Regulation: Inhibitor, Ion;substrate transport  Coupling state: OXPHOS  Pathway: ROX  HRR: Oxygraph-2k 

Labels, 2018-10