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International Journal of Physiology and Pathophysiology
SJR: 0.116

ISSN Print: 2155-014X
ISSN Online: 2155-0158

Archives: Volume 1, 2010 to Volume 9, 2018

International Journal of Physiology and Pathophysiology

DOI: 10.1615/IntJPhysPathophys.v8.i3.50
pages 241-251

Calix[4]arenes as Modulators of Energy- Dependent Ca2+-Accumulation and Functioning of the Electron Transport Chain in Smooth Muscle Mitochondria

Hanna V. Danylovych
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Yuriy V. Danylovych
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Roman V. Rodik
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Victor I. Kalchenko
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Alexander Ju. Chunikhin
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine

ABSTRACT

The effects of supramolecular macrocyclic compounds of calix[4]arenes (C-97, C-99, C-107) at a concentration of 100 nM on the process of energy-dependent Ca2+-transport in isolated mitochondria of smooth muscle, as well as autofluorescence of mitochondrial coenzymes (NADH, FAD), and hydrodynamic diameter of these organelles were investigated. Using Ca2+-sensitive fluorescent dye Fluo-4 AM, it was shown that the selected calix[4]arenes can suppress energy-dependent Ca2+ accumulation by the mitochondria. Accumulation of Ca2+ (80 μM in the medium) is accompanied by the growth of the fluorescent probe response from a conventional unit to a value of (1.57 ± 0.04) (n = 5). Induced by calix[4]arenes C-97, C-99, C-107 fluorescent signal falls below the value of 0.88 ± 0.08, 0.92 ± 0.08, and 0.78 ± 0.04, respectively. Thus, the selected calix[4]arenes evoke a release of previously accumulated Ca2+ from the mitochondria. Under the influence of C-97 and C-99, fluorescent signal from NADH was reduced to -0.11 ± 0.02 and -0.12 ± 0.02, respectively in relation to the reference value of -0.05 ± 0.01 cu (n = 5). An analysis of a fluorescence response of NADH and FAD in suspension of isolated mitochondria suggests that the effects of test compounds on the functional activity of the electron transport chain is associated with the initial stimulation of the 1st complex and subsequent inhibition of Ca2+-dependent NAD-containing Krebs cycle dehydrogenases. Along with this, the use of photon correlation spectroscopy to assess the changes in the mitochondria volume (their hydrodynamic diameter) under the action of selected calix[4]arenes allowed to show that interference with the electron transport chain leads to changes in the osmotic balance between the the mitochondrial matrix and the external environment. The latter result is the growth of isolated organelles volume. In particular, in the presence of C-97 or C-99, the hydrodynamic diameter of mitochondria increased by 22 ± 6% and 34 ± 8%, respectively, (n = 5). Thus, the results obtained indicate that further studies of the calix[4]areneinduced effects on the smooth muscle Ca2+-homeostasis and mitochondrial bioenergetics are reasonable in order to find effective modifiers of their functional activity.