CALIX[4]ARENES С-715 AND С-772 AS INSTRUMENTS OF INFLUENCE ON Са2+-TRANSPORT AND BIOENERGETICS IN MYOMETRIAL MITOCHONDRIA

Abstract

Aim. The goal of work is to study the effects of calix[4]arenes C-715 and C-772 on Ca2+-transport, the electron transport chain activity, and the reactive oxygen species generation in the mitochondria of rat uterine smooth muscle. Methods. Measurement of changes in NADH autofluorescence, as well as the energy-dependent accumulation of Ca2+ and reactive oxygen species generation in the fraction of isolated mitochondria was carried out using the spectrofluorimetry method. The hydrodynamic diameter of mitochondria was measured using the laser correlation spectroscopy method. Results. It was found that calix[4]arenes C-715 and C-772 moderately inhibit both the NADH oxidation and the energy-dependent Ca2+ accumulation by isolated mitochondria. We also showed that the studied calix[4]arenes, depending on concentration and time, reduce the level of reactive oxygen species generation by mitochondria. Additionally, it was revealed that the studied compounds moderately increase mitochondria hydrodynamic diameter depending on concentration. Conclusions. Studied calix[4]arenes slow down the oxidation of NADH in isolated mitochondria, which represents an inhibitory effect on the electron transport chain functioning, in particular its complex I. Since this might lower the electrochemical potential of the inner mitochondrial membrane, we observed reduce of energy-dependent Ca2+ accumulation. Selected compounds decrease the level of reactive oxygen species generation by isolated mitochondria, which could be considered as protective effect on organelles. A moderate increase in mitochondria hydrodynamic diameter suggests that the studied compounds do not cause mitochondrial dysfunction. Researched calix[4]arenes can be used in experimental practice to influence the mitochondrial functional activity.