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Oxydant Stress in the Cardiomyocyte and Its Roles on the Cellular Signaling

Research Project

Project/Area Number 07557343
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Circulatory organs internal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SASAYAMA Shigetake  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (70109007)

Co-Investigator(Kenkyū-buntansha) KIHARA Yasuki  Kyoto University, Graduate School of Medicine, Assistant, 医学研究科, 助手 (40214853)
MATSUMORI Akira  Kyoto University, Graduate School of Med, Instructor, 医学研究科, 講師 (70135573)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsoxygen tension / myocardial ischemia / ATP / E-C coupling / mitochondria / 心筋細胞 / 酸素分圧 / 好気的代謝 / ストレス蛋白 / カルシウム / 酵素分圧 / 虚血 / 再灌流 / 分子生物学
Research Abstract

The tissue oxygen tension is important determinant of the aerobic metabolism. More closely, the tension gradient between the cell surface and the mitochondria might be the more direct regulator of the ATP turnover. Though it has been assumed, the level of intracellular distribution of the oxygen tension in each cell has not been measured yet. In this study, we focused to develop a new system in which the intracellular oxygen distribution was two-dimensionally visualized in a real-time fashion in an isolated single myocyte. The method was derived from the quantification of the regional phosphorescence queching of a phorphilin derivative during the laser excitation on the confocal microscopic apparatus. We have developed a methodology by which the phorphylin derivative was injected into the individual myocyte without significant cellular damage. The study is currently extended to configure the setting of the laser excitation and the data acquisition of the emitted fluorescence in the confocal microscope and the attached computer-based analyzer. The data might provide the essential information of aerobic as well as anaerobic metabolism and the subcellular roles of the oxygen molecule as a transient signal carrier.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Kihara Y,et al.: "Sodium/calcium exchange modulates intracellular calcium overload during-posthypoxic overload overload during posthypoxic reoxygenation in mammalian working myocardium : evidence from aequorin-loaded lerret ventricular muscle." J.Clin.Invest.93. 1275-1284 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "1 Methionine augments myocardial contraction by sensitizing myofilament for calcium." Circ.Res. 77. 80-87 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasayama S,et al.: "Clinical Effects of long-term administration of pimobendan in patients with moderate congestive heart failure" Heart and Vessels.9. 113-120 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "Mechanisms of negative inotropic effects of class Ic antiarrhythimic agents : comparative study of the effects of flecainide and pilsicainide on intracellular calcium in the dog ventricular calcium handling in the dog ventricular myocardium." I.Cardiac.Pharmacolog.27. 42-51 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoko M,et al.: "Trausition from compensatory hypertrophy to dilated,failing left ventricles Dahl salt sensitive rat." Am.J.Physiol.247. H2471-H2482 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoko M,et.al.: "Neurohumoral factors during transition from left ventricular hypertrophy to failnre in Dahl salt-sensitive rats." Biochem.Biophys.Res.Commun.206. 814-820 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morii I,et al.: "A mechanism of negative force-frequency relationship in the physiologically intact rat ventricular myocardium : studies by intracellular Ca^<2+> monitor with indo-1 and by ^<31>P-NMR spectroscopy." Jap.Circ.J.60. 593-603 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "Changes of calcium transients during transitions to heart failure : studies in Dahl rat heart failure model." J.Cardiac.Failure. 2. S113-S120 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisamatsu Y,et al.: "Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats." J.Mol.Cell.Cardiol.29. 1097-1109 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takagi S,et al.: "Slow inactivation of cardiac L-type Ca^<2+> channel induced by cold acclimatization of guinea pig." Am.J.Physiol.274. R348-R356 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morii I,et al.: "Myocarcial contractile effciency and oxygen cost of contractility are preserved during transition from compensated hypertrophy to failure in rats with salt-sensitive hypertension." Hypertension. 31. 946-960 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "Transition from compensatory hypertrophy to dilated failing left ventricle in Dahl-iwai salt-sensitive rats." Am.J.Hypertens. 10. 78S-82S (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwanaga Y,et al.: "Cardiac endothelin-1-plays a critical role in the functional deterioration of left ventricles during the transition from compensatory hypertrophy to congestive heart failure in salt-sensitive hypertensive rats." Circulation. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "Recent Insights into Failing Heart Syndrome" Springer-Verlag,Tokyo, 11 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "Insight Mechanisms and Management" Churchill Livingstone,Tokyo, 8 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 木原康樹: "心不全" 医薬ジャーナル社, 10 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,Sasayama S,Inoko M,Morgan JP.: "Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium : evidence from aequorin-loaded ferret ventricular muscles." J.Clin.Invest.93. 1275-1284 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,Inoko M,Sasayama S.: "1-Methionine augments myocardial contraction by sensitizing myofilament for calcium." Circ.Res.77. 80-87 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sasayama S,Asanoi H,Kihara Y,Yokawa S,Terada Y,Yoshida S,Ejiri M,Horikoshi I.: "Clinical effects of long-term administration of pat pimobendan in ients with moderate congestive heart failure." Heart and Vessels. 9. 113-120 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,Inoko M,Hatakeyama N,Momose Y,Sasayama S.: "Mechanisms of negative inotropic effects of class Ic antiarthythmic. agents : comparative study of the effects of flecainide and pilsicainide on intracellular calcium handling in the dog ventricular myocardium." J.Cardiovasc.Pharmacolog.27. 42-51 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoko M,Kihara Y,Fujiwara H,Sasayama S.: "Transition from compensatory hypertrophy to dilated, failing left ventricles in Dahl salt-sensitive rats." Am.J.Physiol.267. H2471-H2482 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoko M,Kihara Y,Sasayama S.: "Neurohumoral factors during transition from left ventricular hypertrophy to failure in Dahl salt-sensitive rats." Biochem.Biophys. Res.Commun.206. 814-820 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morii I,Kihara Y,Konishi T,Inubushi T,Sasayama S.A: "mechanism of negative force-frequency relationship in the physiologically intact rat ventricualr myocardium : studies by intracellular Ca^<2+> monitor with indo-1 and by ^<31>P-NMR spectroscopy." Jap.Circ.J.60. 593-603 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,Inoko M,Sasayama S.: "Changes of calcium transients during transitions to heart failure : studies in Dahl rat heart failure model." J.Cardiac Failure. 2. S113-S120 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisamatsu Y,Ohkusa T,Kihara Y,Inoko M,Ueyama T,Yano M,Sasayama S,Matsuzaki M.: "Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats." J.Mol.Cell Cardiol.29. 1097-1109 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shioi T,Matsumori A,Kihara Y,Inoko M,Ono K,Iwanaga Y,Yamada T,Iwasaki A,Matsushima K,Sasayama S.: "Increased expression of interleukin-1beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload." Circ.Res.81. 664-671 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takagi S,Kihara Y,Wang Z,Mitsuie T,Noma A,Sasayama S.: "Effects of tilisolol, a non-selective beta-adrenergic bolocker, on the membrane currents of the isolated guinea-pig ventricular myocyte." J.Cardiovascular Pharmacol.29. 593-598 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takagi S,Kihara Y,Sasayama S,Mitsuie T.: "Slow inactivation of cardiac L-type Ca^<2+> channel induced by cold acclimatization of guinea pig." Am.J.Physiol.274. R348-R356 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morii I,Kihara Y,Inoko M,Sasayama S.: "Myocardial contractile efficiency and oxygen cost of contractility are preserved during transition from compensated hypertrophy to failure in rats with salt-sensitive hypertension." Hypertension. 31. 949-960 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,Sasayama S.: "Transition from compensatory hypertrophy to dilated failing left ventricle in Dahl-Iwai salt-sensitive rats." Am.J.Hypertens.10. 78S-82S (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka T,Hasagawa K,Fujita M,Tamaki S,Yamazata A,Kihara Y,Nohara R,Sasayama S.: "Marked elevation of brain natriuretic peptide levels in pericardial fluid is closely associated with left ventricular dysfunction." J.Am.Col.Cardiol.31. 399-403 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y.: "The anti arrhythmic effects and the negative inotropic effects of class Ic agents do not share the common underlying mechanism : the interaction with L-type calcium channel is important" Ion Channel Modulators ID Research Alert.2. 285-288 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kihara Y,et al.: "1-Methionine augments myocardial contraction by sensitizing myofilament for calcium." Ciro.Res.77. 80-87 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kihara Y,et al.: "Mechanisms of negative inotropic effects of class Ic antiarrhythmic agents : comparative study of the effects of flecainide and pilsicainide on intracellular calcium handling in the dog ventricular myocar dium." J.Cardiovase.Pharmacolog.27. 42-51 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morii I,et al.: "A mechanism of negative forcefrequency relationship in the physiologically intace rat ventricular myocardium : studies by intracellular Ca^<2+> monitor iwth indo-1 and by ^<31>P-NMR spectroscopy." Jap.Circ.J.60. 593-603 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kihara Y,et al.: "hanges of calcium transients during transitions to heart failure in Dahl rat heart failure model." J.Cardiac Failure. 2. S113-S120 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hisamatsu Y,et al.: "Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats." J.Mol.Cell.Cardiol.(in press). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takagi S,et al.: "Effects of tilisolol,a nonselective beta-adrenergic blocker,on the membrance currents of the isolated guinea-pig ventricular myocyte." J.Cardiovascular Pharmacol.(in press). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kihara Y,et al.: "Recent Insights into Failing Heart Syndrome" Springer-Verlag,Tokyo, 11 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kihara Y,et al.: "International Nisoldipine Symposium Kyoto'95" Excepta Medica,Ltd.,Tokyo, 13 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kihara Y, Sasayama S,Inoko M, Morgan JP.: "Sodium/Calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium: evidence from aequorin-loaded ferret ferret ventricular muscles." J. Clin. Invest. 93. 1275-1284 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kihara Y, Sasayama S.: "1-Methionine augments myocardial contraction by sensitizing myofilament for calcium" Circ. Res. 77. 80-87 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sasayama S, Asanoi H, Kihara Y, Yokawa S, et al.: "Clinical effects of long-term administration of pimobendan in patients with moderate-congestive heart failure." Heart and Vessels. 9. 120-133 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kihara Y, Inoko M, Hatakeyama N, et al.: "Mechanisms of negative inotropic effects of class Ic antiarrhythmic agents: comparative sutdy of the effects of flecainide and pilsicainide on intracellular calcium handling in the dog" J. Cardiovasc. Pharmacolog.27. 42-51 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inoko M, Kihara Y, Fujiwara H, Sasayama S.: "Transition from compensatory hypertrophy to dilated, failing left ventricles in Dahl salt-sensitive rats." Am. J. Physiol. 267. H2471-H2482 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inoko M, Kihara Y, Sasayama S.: "Neurohumoral factors during transition from left ventricular hypertrophy to failure in Dahl salt-sensitive rats" Biochem. Biophys. Res. Commun.206. 814-820 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sasayama S, Asanoi H, et al.: "Diastolic Relaxation of The Heart, 2nd Edition, Kluwer Academic Publishers" Grossman W. and Lorell BH, des., 8 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kihara Y, Sasayama S: "Proceedings of Oji International Seminar on the Pathophysiological Roles of Intracellular Calcium Ion." Kusuoka H and Marban E, eds., 5 (1994)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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