The role of mitochondria in NO-dependent regulation of Na+, K+ -ATP activity in the rat aorta
| Autor: | O. V. Akopova, Kotsiuruba Av, Iu P Korkach, Sahach Vf, O M Kharlamova |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Physiology ATPase Sodium-Potassium-Exchanging ATPase Oxidative phosphorylation Biology Mitochondrion Mitochondrial membrane transport protein Endocrinology Mitochondrial permeability transition pore Mitochondrial matrix Internal medicine medicine biology.protein Biophysics Heart metabolism |
| Zdroj: | Fiziolohichnyĭ zhurnal. 56:76-85 |
| ISSN: | 2522-9036 2522-9028 |
| DOI: | 10.15407/fz56.04.076 |
| Popis: | In experiments in vivo we studied the interaction between two ion-transporting mechanisms of cardiovascular system--Na+, K+ -ATPase of rat aorta and Ca2+ -uptake system of mitochondria in short-term response to different doses of NO donor, nitroglycerine (NG). The activity of the Na+, K+ -ATPase was determined in rat aorta, and mitochondrial uptake of Ca2+ was studied in rat heart mitochondria assuming that metabolism induced by NO in cardiac mitochondria is similar to that in rat aortic mitochondria. The data show a coordinated dose-dependent action of NG on Na+, K+ -ATPase activity as well as Ca2+ -uptake in mitochondria. An activation of Na+, K+ -ATPase by low dose of NG (0.25 mg/kg body weight) is accompanied by the activation of Ca2+ -uptake in mitochondria as a result of inhibition of permeability transition pore. However, further increase of the dose of the drug leads to reciprocal changes of studied parameters: the decrease in Na+ -pump activity below the control level and the increase of Ca2+ -uptake in mitochondria with a peak at 1.0 mg/kg NG, which takes place in parallel with the dramatic rise in the level of ROS and RNS together with their toxic products, nitrosothiols (NT) and free iron (Fe2+) content in mitochondria. Strong correlation between Ca2+ -uptake and Fe2+ -release, Fe2+ -release and OH-radical formation, the rise in OH-radical level and the decrease of that of H2O2 and mitochondrial NT together with the inhibition of Na+, K+ -ATPase favor a hypothesis that oxidative stress in rat aorta is of mitochondrial origin due to an enhanced uptake of Ca2+ into mitochondrial matrix, Fe2+ deliverance and manifold increase in OH-radical formation from decomposition of hydroperoxide in Haber-Weiss reaction and the decomposition of mitochondrial NT via formation of peroxynitrite, both catalysed by Fe2+, with subsequent release of *OH-radical. Effective abolition of Na+, K+ -ATPase inhibition by potent antioxidant melatonine gives the evidence of the oxidative nature of Na+, K+ -ATPase inhibition by nitric oxide in rat aorta. |
| Databáze: | OpenAIRE |
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