Cyclosporine A attenuates mitochondrial permeability transition and improves mitochondrial respiratory function in cardiomyocytes isolated from dogs with heart failure
| Autor: | Hani N. Sabbah, Sanjaya Khanal, Victor G. Sharov, Anastassia Todor, Makoto Imai |
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| Rok vydání: | 2007 |
| Předmět: |
Cell Respiration
In Vitro Techniques Mitochondrial Membrane Transport Proteins Article Mitochondria Heart Mitochondrial membrane transport protein chemistry.chemical_compound Dogs Sarcolemma Cyclosporin a Animals Myocyte Myocytes Cardiac Respiratory function Molecular Biology Heart metabolism Heart Failure Membrane Potential Mitochondrial biology Mitochondrial Permeability Transition Pore Cell biology Calcein Disease Models Animal Mitochondrial permeability transition pore chemistry Biochemistry Cyclosporine biology.protein Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 42:150-158 |
| ISSN: | 0022-2828 |
| Popis: | We used isolated cardiomyocytes to investigate a possible role of mitochondrial permeability transition pore in mitochondrial abnormalities associated with heart failure. Cardiomyocytes were isolated from LV myocardium of normal control dogs and dogs with heart failure produced by intracoronary microembolizations. Mitochondrial permeability transition was measured in isolated cardiomyocytes with intact sarcolemma with and without 0.2 microM cyclosporin A using calcein AM and the fluorometer. State-3 mitochondrial respiration was also measured with the Clark electrode. Mitochondrial membrane potential was measured with JC-1 probe using the fluorometer. Propidium iodide was used to ensure sarcolemma integrity. 200 min after loading with calcein AM, mitochondria of failing cardiomyocytes showed only 50% of maximal level of calcein fluorescence while it remained unchanged in normal cells. The mitochondrial membrane potential in failing cardiomyocytes was significantly decreased by 38% compared to normal cardiomyocytes. Cyclosporine A significantly slowed the exit of calcein from mitochondria of failing cardiomyocytes and increased mitochondrial membrane potential by 29%. State-3 respiration was not affected with cyclosporine A in normal cardiomyocytes while it was significantly increased in failing cardiomyocytes by 20%. Exit of calcein (m.w. 1.0 kDa) from mitochondria of viable failing cardiomyocytes with intact sarcolemma suggests an existence of a reversible transitory permeability transition opening in high conductance mode. Attenuation of calcein exit, DeltaPsi(m) and improvement of state-3 respiration achieved with CsA (0.2 microM) show that permeability transition opening could be a cause of mitochondrial dysfunction described in the failing heart. |
| Databáze: | OpenAIRE |
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