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

• Nagasaka Shiro

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

• Katoh Hideki

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

• Niu Chun Feng

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

• Matsui Saori

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

• Urushida Tsuyoshi

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

• Satoh Hiroshi

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

• Watanabe Yasuhide

  Department of Basic Nursing, Hamamatsu University School of Medicine

• Hayashi Hideharu

  Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine

抄録

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; 100 μmol/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: 1 μmol/L) but not by an inhibitor of mitochondrial permeability transition pore (mPTP), cyclosporine A (100 nmol/L). Conclusions PKA _cat alters FAD and Δψ_m via mitochodrial ROS generation, and PKA_cat-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. (Circ J 2007; 71: 429 - 436)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 71 (3), 429-436, 2007

  一般社団法人 日本循環器学会

キーワード

• Inner membrane anion channel
• Mitochondrial membrane potential
• Mitochondrial respiratory chain
• Protein kinase A
• Reactive oxygen species

詳細情報

• CRID: 1390282680082511104
• NII論文ID: 110006224216
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.71.429
• COI: 1:CAS:528:DC%2BD2sXjsF2ktL8%3D
• ISSN: 13474820
• ISSN: 13469843
• HANDLE: 10271/1881
• PubMed: 17322647
• Web Site: https://hama-med.repo.nii.ac.jp/records/1848
• Web Site: http://www.jstage.jst.go.jp/article/circj/71/3/71_3_429/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007232699
• 本文言語コード: en
• データソース種別:
  • JaLC
  • IRDB
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可