Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species
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概要
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Background The identification of protein kinase A(PKA) anchoring proteins on mitochondria implies a direct effect of PKA on mitochondrial function. However, little is known about the relationship between PKA and mitochondrial metabolism. Methods and Results The effects of PKA on the mitochondrial redox state(flavin adenine dinucleotide(FAD)), mitochondrial membrane potential(ΔΨ_m) and reactive oxygen species(ROS) production were investigated in saponin-permeabilized rat cardiomyocytes. The PKA catalytic subunit(PKA_<cat>; 50 unit/ml) increased FAD intensities by 56.6±7.9%(p<0.01), 2'7'-dichlorofluorescin diacetate(DCF) intensities by 10.5±3.3 fold(p<0.01) and depolarized ΔΨ_m to 48.1±9.5% of the control(p<0.01). Trolox(a ROS scavenger; 100μmol/L) inhibited PKA_<cat>-induced ΔΨ_m, FAD and DCF alteration. PKA_<cat>-induced ΔΨ_m depolarization was inhibited by an inhibitor of the inner membrane anion channel(IMAC), 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid(DIDS: 1μmol/L) but not by an inhibitor of mitochondrial permeability transition pore(mPTP), cyclosporine A(lOOnmol/L). Conclusions PKA_<cat> alters FAD and ΔΨ_m via mitochodrial ROS generation, and PKAcat-induced ΔΨ_m depolarization was not caused by mPTP but rather by DIDS-sensitive mechanisms, which could be caused by opening of the IMAC. The effects of PKA on mitochondrial function could be related to myocardial function under the condition of extensive β-adrenergic stimulation.
- 2007-02-20
著者
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Satoh Hiroshi
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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URUSHIDA Tsuyoshi
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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KATOH Hideki
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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HAYASHI Hideharu
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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Wakabayashi Yasushi
Department of Medicine III, Hamamatsu University School of Medicine
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Katoh Hideki
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Internal Medicine Iii Hamamatsu University School Of Medicine
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Urushida Tsuyoshi
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Wakabayashi Yasushi
Department Of Basic Nursing Hamamatsu University School Of Medicine
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Hayashi Hideharu
Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Niu Chun
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Watanabe Yasuhide
Department of Basic Nursing, Hamamatsu University School of Medicine
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Nagasaka Shiro
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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Niu Chim
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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Matsui Saori
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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Nagasaka Sirou
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Watanabe Yasuhide
Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
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Matui Saori
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Watanabe Yasuhide
Department Of Pharmacology School Of Medicine Fukushima Medical University
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Sone Hirohito
Department Of Nutrition Ochanomizu University
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Wakabayashi Yasushi
Department Of Pharmacology School Of Medicine Fukushima Medical University
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Nagasaka Shiro
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Matsui Saori
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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