Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter
BACKGROUND AND AIMS: Cardiac mitochondrial Ca(2+) overload plays a critical role in mechanical and electrical dysfunction leading to cardiac cell death and fatal arrhythmia. Because Ca(2+) overload is related to mitochondrial permeability transition, reactive oxygen species (ROS) production and memb...
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th-cmuir.6653943832-38592014-08-30T02:35:24Z Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter Yarana C. Sripetchwandee J. Sanit J. Chattipakorn S. Chattipakorn N. BACKGROUND AND AIMS: Cardiac mitochondrial Ca(2+) overload plays a critical role in mechanical and electrical dysfunction leading to cardiac cell death and fatal arrhythmia. Because Ca(2+) overload is related to mitochondrial permeability transition, reactive oxygen species (ROS) production and membrane potential (ΔΨm) dissipation, we probed the mechanistic association between Ca(2+) overload, oxidative stress, mitochondrial permeability transition pore (mPTP) and mitochondrial calcium uniporter (MCU) in isolated cardiac mitochondria. METHODS: Various concentrations of Ca(2+) (5-200 μM) were used to induce mitochondrial dysfunction. Cyclosporin A (CsA, an mPTP blocker) and Ru360 (an MCU blocker) were used to test its protective effects on Ca(2+)-induced mitochondrial dysfunction. RESULTS: High concentrations of Ca(2+) (≥100 μM) caused overt mitochondrial swelling and ΔΨm collapse. However, only slight increases in ROS production were detected. Blocking the MCU by Ru360 is less effective in protecting mitochondrial dysfunction. CONCLUSIONS: A dominant cause of Ca(2+)-induced cardiac mitochondrial dysfunction was mediated through the mPTP rather than MCU. Therefore, CsA could be more effective than Ru360 in preventing Ca(2+)-induced cardiac mitochondrial dysfunction. 2014-08-30T02:35:24Z 2014-08-30T02:35:24Z 2012 JOURNAL ARTICLE 1873-5487 22824212 http://www.ncbi.nlm.nih.gov/pubmed/22824212 http://cmuir.cmu.ac.th/handle/6653943832/3859 ENG |
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BACKGROUND AND AIMS: Cardiac mitochondrial Ca(2+) overload plays a critical role in mechanical and electrical dysfunction leading to cardiac cell death and fatal arrhythmia. Because Ca(2+) overload is related to mitochondrial permeability transition, reactive oxygen species (ROS) production and membrane potential (ΔΨm) dissipation, we probed the mechanistic association between Ca(2+) overload, oxidative stress, mitochondrial permeability transition pore (mPTP) and mitochondrial calcium uniporter (MCU) in isolated cardiac mitochondria. METHODS: Various concentrations of Ca(2+) (5-200 μM) were used to induce mitochondrial dysfunction. Cyclosporin A (CsA, an mPTP blocker) and Ru360 (an MCU blocker) were used to test its protective effects on Ca(2+)-induced mitochondrial dysfunction. RESULTS: High concentrations of Ca(2+) (≥100 μM) caused overt mitochondrial swelling and ΔΨm collapse. However, only slight increases in ROS production were detected. Blocking the MCU by Ru360 is less effective in protecting mitochondrial dysfunction. CONCLUSIONS: A dominant cause of Ca(2+)-induced cardiac mitochondrial dysfunction was mediated through the mPTP rather than MCU. Therefore, CsA could be more effective than Ru360 in preventing Ca(2+)-induced cardiac mitochondrial dysfunction. |
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Yarana C. Sripetchwandee J. Sanit J. Chattipakorn S. Chattipakorn N. |
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Yarana C. Sripetchwandee J. Sanit J. Chattipakorn S. Chattipakorn N. Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter |
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Yarana C. Sripetchwandee J. Sanit J. Chattipakorn S. Chattipakorn N. |
author_sort |
Yarana C. |
title |
Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter |
title_short |
Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter |
title_full |
Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter |
title_fullStr |
Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter |
title_full_unstemmed |
Calcium-induced Cardiac Mitochondrial Dysfunction Is Predominantly Mediated by Cyclosporine A-dependent Mitochondrial Permeability Transition Pore But Not Mitochondrial Calcium Uniporter |
title_sort |
calcium-induced cardiac mitochondrial dysfunction is predominantly mediated by cyclosporine a-dependent mitochondrial permeability transition pore but not mitochondrial calcium uniporter |
publishDate |
2014 |
url |
http://www.ncbi.nlm.nih.gov/pubmed/22824212 http://cmuir.cmu.ac.th/handle/6653943832/3859 |
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1681420128106840064 |