Tag Archives: cardiomyocytes
Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes
S. M. Korotkov, V. P. Nesterov, G. B. Belostotskaya,
I. V. Brailovskaya, A. V. Novozhilov, C. V. Sobol
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russian Federation;
e-mail: korotkov@SK1645.spb.edu
Received: 05 September 2019; Accepted: 29 November 2019
Thallium is known to produce one of the most complex and serious patterns of toxicity, involving a wide range of human organs and tissues. The toxic impact on biologic organisms is linked especially to the ability of Tl+ to disturb calcium homeostasis and to permeate easily the inner mitochondrial membrane (IMM). The aim of this work was to study the effects of Tl+ on intracellular Ca2+ dynamics in rat neonatal cardiomyocytes as well as on sodium penetrability of the IMM and Tl+-induced mitochondrial permeability transition pore (MPTP) opening in isolated Ca2+-loaded rat heart mitochondria (RHM). The use of the fluorescent calcium indicator Fura 2 AM showed that Tl+ induced calcium influx across the plasmatic membrane, resulting in calcium ([Ca2+]i) increase in the cytoplasm. This increase was even more pronounced in experiments with accelerating of Tl+-transmembrane fluxes by nonactin. It was nevertheless abolished by the removal of extracellular Ca2+ ions, but was not inhibited by a calcium-channel blocker (nifedipine). Tl+ did not release calcium from the intracellular stores. Tl+ potentiated sodium permeability of the IMM because swelling of nonenergized RHM in medium containing TlNO3 and NaNO3 was enhanced at high Tl+ concentration. The calcium load of RHM induced MPTP opening which was accompanied by the increase of the swelling as well as the decrease of the inner membrane potential and of state 40 (basal) and state 3UDNP (2,4-dinitrophenol-uncoupled) respiration. These effects of Tl+ were suppressed by MPTP inhibitors (cyclosporine A, ADP and n-ethylmaleimide). The data obtained showed that Tl+-stimulated influx of extracellular calcium into cardiomyocytes could cause calcium and sodium RHM overload, which lead to the MPTP opening, thus determining the sensitivity of heart muscle to thallium intoxication.
The effect of quercetin on oxidative stress markers and mitochondrial permeability transition in the heart of rats with type 2 diabetes
N. I. Gorbenko1, O. Yu. Borikov2, O. V. Ivanova1, E. V. Taran1,
Т. S. Litvinova1, T. V. Kiprych1, A. S. Shalamai3
1V. Danilevsky Institute of Endocrine Pathology Problems, National Academy of Medical Sciences of Ukraine, Kharkiv;
2V. N. Karazin Kharkiv National University, Ukraine;
3PJSC SIC “Borshchahivskiy Chemical-Pharmaceutical Plant”, Kyiv, Ukraine;
е-mail: Gorbenkonat58@ukr.net
Received: 24 June 2019; Accepted: 13 August 2019
Increasing evidence suggests that oxidative stress and induction of mitochondrial permeability transition in cardiomyocytes are linked to tissue damage and the development of diabetic cardiovascular complications. The aim of this study was to assess the effects of quercetin (Q) on oxidative stress and mitochondrial permeability transition in the heart of rats with type 2 diabetes mellitus (DM). Type 2 DM was induced in 12-week-old male Wistar rats by intraperitoneal injections of 25 mg/kg streptozotocin twice per week followed by a high-fat diet during four weeks. The rats were divided into three groups: control intact group (C, n = 8), untreated diabetic group (Diabetes, n = 8) and diabetic rats treated with Q (50 mg/kg/day per os for 8 weeks) after diabetes induction (Diabetes+Q, n = 8). Administration of Q increased insulin sensitivity and normalized the functional state of cardiac mitochondria due to increased aconitase and succinate dehydrogenase activities in rats with type 2 DM. Q also ameliorated oxidative stress, decreasing the level of advanced oxidation protein products and increasing the activity of thioredoxin-reductase in heart mitochondria of diabetic rats. In addition, Ca2+-induced opening of the mitochondrial permeability transition pore was significantly inhibited in diabetic rats treated with Q in comparison with the untreated diabetic group. These data demonstrate that Q can protect against oxidative stress, mitochondrial permeability transition induction and mitochondrial dysfunction in cardiomyocytes of diabetic rats. We suggest that the use of Q may contribute to the amelioration of cardiovascular risk in type 2 DM.
RNA interference of proteasome subunit of PSMβ7 gene restricts proteasome subunit PSMβ1 and PSMβ5 mRNA expression and peptidyl-glutamyl peptide-hydrolyzing proteasome activity in neonatal cardiomyocytes
V. O. Kyrychenko, D. O. Pashevin, L. V. Tumanovska, V. E. Dosenko, O. O. Moibenko
Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;
e-mail: victoria30@mail.ru
Using small interfering RNA (siRNA) transfection of neonatal cardiomyocytes to inhibit expression of nonproteolytic proteasome β7 subunit, we observed a significant decrease in β1 proteolytic subunit mRNA expression. Proteasome peptidyl-glutamyl peptide-hydrolyzing activity decreased to 28% (0.48 ± 0.2 nM AMC/min) compared to control (1.7 ± 0.5 nM AMC/min) (Р < 0.05). β5 Subunit mRNA expression decreased 21 times (Р < 0.05) with no changes in its chymotrypsin-like activity. Proteasome trypsin-like activity and activity of another proteolytic enzyme tripeptidylpeptidase II remained unchanged.
Fatty acids composition of inner mitochondrial membrane of rat cardiomyocytes and hepatocytes during hypoxia-hypercapnia
S. V. Khyzhnyak, S. V. Midyk, S. V. Sysoliatin, V. М. Voitsitsky
National University of Life and Environmental Sciences of Ukraine, Kyiv;
е-mail: khs2014@ukr.net
We studied the influence of hypoxic-hypercapnic environment under the effect of hypothermia (artificial hibernation) on fatty acids spectrum of inner mitochondrial membrane (IMM) lipids of rat cardiomyocytes and hepatocytes. Specific for cellular organelles redistribution of IMM fatty acids was determined. It led to the reduction of total amount of saturated fatty acids (SFAs) and increase of unsaturated fatty acids (UFAs) in cardiomyocytes and to the increase of SFAs and decrease of UFAs in hepatocytes. The decrease in the content of oleic acid and increased content of arachidonic and docosahexaenoic acids in IMM were shown. This may be due to their role in the regulatory systems during hibernation, as well as following exit therefrom. It is assumed that artificial hibernation state is characterized by the stress reaction leading to optimal readjustment of fatty acids composition of membrane lipids, which supports functional activity of mitochondria in hepatocytes and cardiomyocytes.