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1.
Bull Exp Biol Med ; 170(4): 431-435, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33725242

ABSTRACT

We have previously demonstrated that the development of oxidative stress in some pathologies can be prevented by activation of the mitochondrial ATP-dependent potassium channel (mitoKATP). Here we studied the effect of modulation of mitoKATP on the development of mitochondrial and endothelial dysfunction in the medulla oblongata and myocardium of rats with experimental parkinsonism. It is known that uridine-5'-diphosphate, activator of mitoKATP, does not penetrate the plasma membrane, but it can be synthesized in cells from exogenous uridine that is delivered into cells by special transport systems. Our results suggest that mitoKATP is involved in the development of mitochondrial and endothelial dysfunction in experimental parkinsonism and prove the cardio- and neuroprotective effects of uridine.


Subject(s)
Parkinsonian Disorders/metabolism , Potassium Channels/metabolism , Adenosine Triphosphate/metabolism , Animals , Male , Mitochondria/drug effects , Mitochondria/metabolism , Myocardium/metabolism , Rats , Rats, Wistar , Rotenone/metabolism , Uridine/metabolism
2.
Biochemistry (Mosc) ; 80(8): 994-1000, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26547067

ABSTRACT

The ultrastructure and spatial localization of mitochondria (MC) in the myocardium of rats exposed to a 30-min hypoxic hypoxia were investigated. The mitochondrial structure was found to undergo changes; however, marked necrotic injuries were not observed. Changes occurring in the myocardium are aimed at the intensification of energy processes. This shows up as an increase in the number of MC in the subsarcolemmal zone of the myocardium and changes in the surface of the sublemmal membrane due to its bending around mitochondria, which improves the diffusion of oxygen into MC. In addition, the division of MC is enhanced, which partially explains the increase in their total number. In structurally altered MC with intact membrane, electron dense formations with small diameter appear, which probably represent newly formed organelles (microMC). In normoxia, changes of this kind do not occur. It was found that the ATP-dependent K+ channel is involved in the regulation of the morphological state of MC under hypoxic hypoxia. The activator of the channel diazoxide increases the number of newly formed microMC, and the channel inhibitor 5HD significantly prevents their formation. Possible mechanisms of structural and dynamic changes in rat myocardial MC under acute hypoxic hypoxia are discussed.


Subject(s)
Cell Hypoxia/drug effects , Hypoxia/metabolism , Mitochondria, Heart/metabolism , Mitochondria, Heart/ultrastructure , Adenosine Triphosphate/metabolism , Animals , Male , Myocardium/metabolism , Potassium Channel Blockers/pharmacology , Potassium Channels/metabolism , Rats , Rats, Wistar , Spatial Analysis
3.
Biochemistry (Mosc) ; 78(1): 80-90, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23379563

ABSTRACT

The effect of potential-dependent potassium uptake at 0-120 mM K+ on matrix Ca2+ accumulation in rat brain mitochondria was studied. An increase in oxygen consumption and proton extrusion rates as well as increase in matrix pH with increase in K+ content in the medium was observed due to K+ uptake into the mitochondria. The accumulation of Ca2+ was shown to depend on K+ concentration in the medium. At K+ concentration ≤30 mM, Ca2+ uptake is decreased due to K+-induced membrane depolarization, whereas at higher K+ concentrations, up to 120 mM K+, Ca2+ uptake is increased in spite of membrane depolarization caused by matrix alkalization due to K+ uptake. Mitochondrial K+(ATP)-channel blockers (glibenclamide and 5-hydroxydecanoic acid) diminish K+ uptake as well as K+-induced depolarization and matrix alkalization, which results in attenuation of the potassium-induced effects on matrix Ca2+ uptake, i.e. increase in Ca2+ uptake at low K+ content in the medium due to the smaller membrane depolarization and decrease in Ca2+ uptake at high potassium concentrations because of restricted rise in matrix pH. The results show the importance of potential-dependent potassium uptake, and especially the K+(ATP) channel, in the regulation of calcium accumulation in rat brain mitochondria.


Subject(s)
Brain/cytology , Brain/metabolism , Calcium/metabolism , Mitochondria/metabolism , Potassium/metabolism , Animals , Rats , Rats, Wistar
4.
Biochemistry (Mosc) ; 75(9): 1139-47, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21077833

ABSTRACT

The influence of the K+(ATP)-channel opener diazoxide on the K+ cycle and oxygen consumption has been studied in rat liver mitochondria. It was found that diazoxide activates the K+(ATP)-channel in the range of nanomolar concentrations (50-300 nM, K(1/2) ~ 140 nM), which results in activation of K+/H+ exchange in mitochondria. The latter, in turn, accelerates mitochondrial respiration in respiratory state 2. The contribution of K+(ATP)-channel to the mitochondrial potassium cycle was estimated using the selective K+(ATP)-channel blocker glibenclamide. The data show that the relative contribution of K+(ATP)-channel in the potassium cycle of mitochondria is variable and increases only with the decrease in the ATP-independent component of K+ uptake. Possible mechanisms underlying the observed phenomena are discussed. The experimental results more fully elucidate the role of K+(ATP)-channel in the regulation of mitochondrial functions, especially under pathological conditions accompanied by impairment of the mitochondrial energy state.


Subject(s)
Adenosine Triphosphate/metabolism , KATP Channels/metabolism , Mitochondria, Liver/metabolism , Potassium/metabolism , Animals , Diazoxide/pharmacology , Glyburide/pharmacology , Oxygen Consumption , Potassium Channel Blockers/pharmacology , Rats , Rats, Wistar
5.
Biochemistry (Mosc) ; 73(10): 1146-53, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18991562

ABSTRACT

The influence of potassium ions on calcium uptake in rat liver mitochondria is studied. It is shown that an increase in K+ and Ca2+ concentrations in the incubation medium leads to a decrease in calcium uptake in mitochondria together with a simultaneous increase in potassium uptake due to the potential-dependent transport of K+ in the mitochondrial matrix. Both effects are more pronounced in the presence of an ATP-dependent K+-channel (K+(ATP)-channel) opener, diazoxide (Dz). Activation of the K+(ATP)-channel by Dz alters the functional state of mitochondria and leads to an increase in the respiration rate in state 2 and a decrease in the oxygen uptake and the rate of ATP synthesis in state 3. The effect of Dz on oxygen consumption in state 3 is mimicked by valinomycin, but it is opposite to that of the classical protonophore uncoupler CCCP. It is concluded that the potential-dependent uptake of potassium is closely coupled to calcium transport and is an important parameter of energy coupling responsible for complex changes in oxygen consumption and Ca2+-transport properties of mitochondria.


Subject(s)
Adenosine Triphosphate/metabolism , Calcium/metabolism , KATP Channels/metabolism , Mitochondria, Liver/metabolism , Animals , Carbonyl Cyanide m-Chlorophenyl Hydrazone/metabolism , Kinetics , Oxygen Consumption/physiology , Potassium/metabolism , Rats , Rats, Wistar
6.
High Alt Med Biol ; 1(2): 105-10, 2000.
Article in English | MEDLINE | ID: mdl-11256561

ABSTRACT

The study was undertaken to elucidate the effects of taurine on lipid peroxidation (LP) intensity and membrane Na+, K+-ATPase activity in a hypoxic rat model. It was shown that 3 intraperitoneal (i.p.) injections of 200 mg/kg of taurine prevented hypoxia-induced lactate accumulation and LP in brain, liver, and heart tissues and prevented the decrease of Na+, K+-ATPase activity in the liver. It is suggested that the effect of taurine on LP could be due to the taurine antiacidotic action as well as to its membrane stabilizing activity.


Subject(s)
Antioxidants/therapeutic use , Hypoxia/drug therapy , Hypoxia/metabolism , Lipid Peroxidation/drug effects , Sodium-Potassium-Exchanging ATPase/drug effects , Taurine/therapeutic use , Animals , Antioxidants/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Injections, Intraperitoneal , Male , Malondialdehyde/analysis , Rats , Rats, Wistar , Taurine/pharmacology , Tissue Distribution
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