2006 Fiscal Year Final Research Report Summary
mitochondrial function in failed cardiac muscle
| Project/Area Number |
16590671
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KATOH Hideki Hamamatsu University School of Medicine, assistant professor, 医学部, 助教 (80314029)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Hiroshi Hamamatsu University School of Medicine, Senior Associate Professor, 医学部附属病院, 講師 (30293632)
TERADA Hajime Hamamatsu University School of Medicine, Senior Associate Professor, 医学部附属病院, 講師 (50252177)
HAYASHI Hideharu Hamamatsu University School of Medicine, Professor, 医学部, 教授 (50135258)
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| Project Period (FY) |
2004 – 2006
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| Keywords | mitochondria / protein kinase A / membrane potential / heart failure / redox state / reactive oxygen species |
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| Research Abstract |
β-adrenergic stimulation acts via cAMP-dependent protein kinase A (PKA) to phosphorylate functional proteins and myofibrils. However, relatively little is known about the relationship between mitochondrial metabolism and PKA in response to (β-adrenergic stimulation. We investigated the effects of PKA on mitochondrial redox state (FAD fluorescence), mitochondrial membrane potential (ΔΨ_m ; measured with TMRE) and ROS production (measured with dichlorofluorescein diacetate (DCF) fluorescence) in saponin-permeabilized rat ventricular myocytes. (1) Application of PKA catalytic subunit (PKA_<cat>) increased FAD intensities, which was inhibited by a PKA inhibitor (PKI). (2) Application of PKA_<cat> depolarized ΔΨ_m. The effect of PKA_<cat> on ΔΨ_m was blocked by PKI. (3) Application of PKA_<cat> increased DCF intensities, which was inhibited by Trolox (a ROS scavenger). (4) PKA_<cat>-induced ΔΨ_m depolarization and FAD elevation were inhibited by Trolox. (5) PKA_<cat>-induced ΔΨ_m, depolarization was inhibited by DIDS (an inhibitor of inner membrane anion channel (IMAC)) but not by CsA (an mPTP inhibitor). These results demonstrated that PKA_<cat> alters mitochondrial redox state and ΔΨ_m via mitochodrial ROS generation. It is also suggested that PKA-induced ΔΨ_m depolarization was not related to mPTP, but to the DIDS sensitive mechanisms, which could be IMAC. The depolarizaticin of ΔΨ_m by PKA might be related to the mitochondrial dysfunction under the condition of extensive β-adrenergic stimulation.
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