Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species

元データ 2007-02-20

概要

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.

著者

Satoh Hiroshi Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
URUSHIDA Tsuyoshi Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
KATOH Hideki Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
HAYASHI Hideharu Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
Wakabayashi Yasushi Department of Medicine III, Hamamatsu University School of Medicine
Katoh Hideki Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Internal Medicine Iii Hamamatsu University School Of Medicine
Urushida Tsuyoshi Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Wakabayashi Yasushi Department Of Basic Nursing Hamamatsu University School Of Medicine
Hayashi Hideharu Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Niu Chun Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Watanabe Yasuhide Department of Basic Nursing, Hamamatsu University School of Medicine
Nagasaka Shiro Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
Niu Chim Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
Matsui Saori Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
Nagasaka Sirou Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Watanabe Yasuhide Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University
Matui Saori Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Watanabe Yasuhide Department Of Pharmacology School Of Medicine Fukushima Medical University
Sone Hirohito Department Of Nutrition Ochanomizu University
Wakabayashi Yasushi Department Of Pharmacology School Of Medicine Fukushima Medical University
Nagasaka Shiro Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Matsui Saori Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine

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