Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species
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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 (ΔΨm) and reactive oxygen species (ROS) production were investigated in saponin-permeabilized rat cardiomyocytes. The PKA catalytic subunit (PKAcat; 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 ΔΨm to 48.1±9.5% of the control (p<0.01). Trolox (a ROS scavenger; 100μmol/L) inhibited PKAcat-induced ΔΨm, FAD and DCF alteration. PKAcat-induced ΔΨm 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 (100 nmol/L).Conclusions PKAcat alters FAD and ΔΨm via mitochodrial ROS generation, and PKAcat-induced ΔΨm 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 extensiveβ-adrenergic stimulation.rights:社団法人日本循環器学会rights:本文データは学協会の許諾に基づきCiNiiから複製したものであるrelation：isVersionOf:http://ci.nii.ac.jp/naid/110006224216
- THE JAPANESE CIRCULATION SOCIETYの論文
- 2007-02-20
THE JAPANESE CIRCULATION SOCIETY | 論文
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