1990 Fiscal Year Annual Research Report

心筋細胞障害の成因と防御に関する基礎的研究

Research Project

Project/Area Number	02299111
Research Institution	Osaka University
Principal Investigator	多田道彦大阪大学, 医学部, 教授 (90093434)
Co-Investigator(Kenkyū-buntansha)	外山淳治名古屋大学, 環境医学研究所, 教授 (20023658) 河合忠一京都大学, 医学部, 教授 (70025659) 杉本恒明東京大学, 医学部, 教授 (60019883) 戸嶋裕徳久留米大学, 医学部, 教授 (00080664) 中村元臣九州大学, 医学部, 教授 (60037322)
Keywords	心筋細胞障害 / 収筋興奮収縮連関 / イオンチャンネル / 収縮蛋白質 / 細胞情報伝達機構 / 心筋肥大 / 酸素ラジカル / ミトコンドリア遺伝子異常症
Research Abstract	心臓病における心筋細胞障害の成因を明確にし適切な防御を講じる上には心臓機能の基本原理並びにその調節・適応機構の生物学的基盤を究めることが必須であるとの認識から過去3カ年にわたり重点領域研究「心筋細胞障害の成因と防御に関する基礎的研究」を推進してきた。本年度は,かかる研究成果を総括するとともに,細胞・分子レベルでの心筋機能及び病態研究の現時点でのまとめを行うために,本研究班員を含めた国内外の一流の研究者(約200名)による「心臓の分子生物学に関する国際会議」(平成2年度9月16,17日:於大阪)を開催し,以下に述べる学術討論を行った。第一に,心筋機能を司る興奮収縮連関の物質論的基盤を明確にする立場から各種イオン・チャンネル,イオン・ポンプおよび収縮蛋白質の分子レベルでの実体を論じた。これらの蛋白質のいくつかについては,分子生物学的手法により一次構造も判明しており,各蛋白質の構造機能連関という観点からの解析を示した。第二に,心臓では,収縮弛緩の基本機構のみならず,種々の刺激に対する応答機構としての調節系が重要な役割を果たしている。この問題については受容体,GTP結合蛋白質,Ca^<2+>やCAMPをセカンドメッセンジャ-とする情報伝達系の機能蛋白質の分子生理学的解析の最新の成果を紹介した。第三に,心臓における病態解析の代表として,心肥大における収縮蛋白質の遺伝子レベルでの形質変換機構や遺伝性心筋障害におけるミトコンドリア遺伝子異常の解明などを提示した。心臓は生理学的に特別な機能を司るように高度に分化した臓器でもあり,従来のいわゆる細胞生物学の知識のみでは充分理解しがたい側面も数多くみられる。このような観点から最後に細胞分化の問題を取り上げ,今後の研究課題としての提示を試みた。かかる成果の詳細を「Molecular Biology of the Myocardium」(学会出版センタ-)として出版する予定である。

Research Products

(52 results)

All Other

All Publications (52 results)

[Publications] Katano,Y.et al.: "Differential effects of Ro 20ー1724 and isobutylmethylxanthine on the basal force of contraction and betaーadrenoceptorーmediated response in the rat ventricular myocardium." Biochem Biophys Res Commun. 167. 123-129 (1990)
[Publications] Matsubara,I.et al.: "Crossーbridge movement in rat cardiac muscle as a function of calcium concentration." J Physiol. 417. 555-565 (1999)
[Publications] Matsuoka,S.et al.: "Chlorideーsensitive nature of the adrenalineーinduced current in guineaーpig cardiac myocytes." J Physiol. 425. 579-598 (1990)
[Publications] Sugiura,H.et al.: "ATP directly affects junctional conductance between paired ventricular myocytes isolated from guinea pig heart." Circ Res.66. 1095-1102 (1990)
[Publications] Adaniya,H.et al.: "Effects of a novel class III antiarrhythmic agent,Eー4031,on reentrant tachycardias in rabbit right atrium." J Cardiovasc Pharmacol. 15. 976-982 (1990)
[Publications] Wakabayashi,S.et al.: "Mechanism for activation of the 4ーnitrobenzoー2ーoxaー1,3ーdiazoleーlabeled sarcoplasmic reticulum ATPase by Ca2+ and its modulation by nucleotides." Biochemistry. 29. 7309-7318 (1990)
[Publications] Iwai,K.et al.: "Disruption of microtubules as an early sign of irreversible ischemic injury.Immunohistochemical study of in situ canine hearts." Circ Res.67. 694-706 (1990)
[Publications] Kanatsuka,H.et al.: "Diameter change and pressureーred blood cell velocity relations in coronary microvessels during long diastoles in the canine left ventricle." Circ Res.66. 503-510 (1990)
[Publications] Fujitsuka,C.et al.: "Intramembrane particles and responses of sensory axon terminals during reinnervation of the frog muscle spindle." J Neurocytol. 19. 175-186 (1990)
[Publications] Hori,M.et al.: "An increase in myocardial betaーadrenoceptors to compensate for postischaemic dysfunction following coronary microーembolisation in dogs." Gardiovasc Res.23. 423-431 (1990)
[Publications] Tsutsui,H.et al.: "Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits." Circ Res.67. 368-375 (1990)
[Publications] Hamamori,Y.et al.: "5ーHydroxytryptamine induces phospholipase Cーmediated hydrolysis of phosphoinositides through 5ーhydroxytryptamineー2 receptors in cultured fetal mouse ventricular mvocvtes." Circ Res.66. 1474-1483 (1990)
[Publications] Ohta,Y et al.: "Ca2+/calmodulinーdependent protein kinase II:localization in the interphase nucleus and the mitotic apparatus of mammalian cells." Proc Natl Acad Sci USA. 87. 5341-5345 (1990)
[Publications] Hirooka,Y.et al.: "Attenuated forearm vasodilative response to intraーarterial atrial natriuretic peptide in patients with heart failure." Circulation. 82. 147-153 (1990)
[Publications] Komuro,I.et al.: "Molecular cloning of gene sequences from rat heart rapidly responsive to pressure overload." Circ Res.66. 979-985 (1990)
[Publications] Kotaka,M.et al.: "Experimental influenza A virus myocarditis in mice.Light and electron microscopic,virologic,and hemodynamic study." Am J Pathol. 136. 409-419 (1990)
[Publications] Koga,Y.et al.: "Decreased coronary vasodilatory capacity in hypertrophic cardiomyopathy determined by splitーdose thalliumーdipyridamole myocardial scintigraphy." Am J Cardiol. 65. 1134-1139 (1990)
[Publications] Ozawa,T.et al.: "Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy." Biochem Biophys Res Commun. 170. 830-836 (1990)
[Publications] Sato,H.et al.: "Acute hemodynamic effects of nilvadipine,a new calcium channel blocker,in patients with congestive heart failure." J Cardiovasc Pharmacol. 15. 317-322 (1990)
[Publications] Yamamoto,T.et al.: "Purification and characterization from bovine brain cytosol of proteins that regulate the GDP/GTP exchange reaction of smg p21s,ras p21ーlike GTPーbinding proteins." J Biol Chem.265. 16626-16634 (1990)
[Publications] Sumimoto,H.et al.: "Oxidation of 20ーhydroxyleukotriene B4 to 20ーcarboxyleukotriene B4 by human neutrophil microsomes.Role of aldehyde dehydrogenase and leukotriene B4 omegaーhydroxylase (cytochrome Pー450LTB omega) in leukotriene B4 omegaーoxidation." J Biol Chem.265. 4348-4353 (1990)
[Publications] Katori,M.et al.: "Evidence for the involvement of a plasma kallikreinーkinin system in the immediate hypotension produced by endotoxin in anaesthetized rats." Br J Pharmacol. 98. 1383-1391 (1990)
[Publications] Aoyama,T.et al.: "Prostaglandin I2 halfーlife regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris [see comments]." Circulation. 81. 1784-1791 (1990)
[Publications] Matsumoto,T.et al.: "Characteristics of the histamineーsensitive calcium store in vascular smooth muscle.Comparison with norepinephrineーor caffeineーsensitive stores." J Biol Chem. 265. 5610-5616 (1990)
[Publications] Fujita,H.et al: "A specific protein,p92,detected in flat revertants derived from NIH/3T3 transformed by human activated cーHaーras oncogene." Exp Cell Res.186. 115-121 (1990)
[Publications] Tona,L.et al.: "Depressant effects of chloroquine on the isolated guineaーpig heart." Eur J Pharmacol.178. 293-301 (1990)
[Publications] Kasanuki,H.et al.: "Differentiation and mechanisms of prevention and termination of verapamilーsensitive sustained ventricular tachvcardia." Am J Cardiol. 64. 46J-49J (1990)
[Publications] Yoshimoto,T.et al.: "Cloning and sequence analysis of the cDNA for arachidonate 12ーlipoxygenase of porcine leukocytes." Proc Natl Acad Sci USA. 87. 2142-2146 (1990)
[Publications] Nanto,S.et al.: "Percutaneous transluminal coronary angioplasty using kissing balloon technique in the left main trunk." Heart Vessels. 5. 107-112 (1990)
[Publications] Imaizumi,T.et al.: "Limited maximal vasodilator capacity of forearm resistance vessels in patients with hypertrophic cardiomyopathy." Heart Vessels.5. 159-165 (1990)
[Publications] Iijima,T.et al.: "Differential modulation by beta adrenoceptors of inward calcium and delayed rectifier potassium current in single ventricular cells of guinea pig heart." J Pharmacol Exp Ther. 254. 142-146 (1990)
[Publications] Kodama,I.et al.: "Two types of sodium channel block by classーI antiarrhythmic drugs studied by using Vmax of action potential in single ventricular myocytes." J Mol Cell Cardiol. 22. 1-12 (1990)
[Publications] Oike,M.et al: "Dual action of FRC8653,a novel dihydropyridine derivative,on the Ba2+ current recorded from the rabbit basilar artery." Circ Res. 67. 993-1006 (1990)
[Publications] Takuwa,Y.et al.: "Endothelin receptor is coupled to phospholipase C via a pertussis toxinーinsensitive guanine nucleotideーbinding regulatory protein in vascular smooth muscle cells." J Clin Invest. 85. 653-658 (1990)
[Publications] Kawaguchi,H.et al.: "Plateletーactivating factor stimulates angiotensin converting enzyme activity." J Hypertens. 8. 173-177 (1990)
[Publications] Okumura,K.et al.: "Norepinephrineーinduced 1,2ーdiacylglycerol accumulation and change in its fatty acid composition in the isolated perfused rat heart." Mol Cell Biochem. 93. 173-178 (1990)
[Publications] Nakamura,Y.et al.: "Comparative study of cell saver and ultrafiltration nontransfusion in cardiac surgery." Ann Thorac Surg. 49. 973-978 (1990)
[Publications] Takami,H.et al.: "Leakage of cytoplasmic enzymes from rat heart by the stress of cardiac beating after increase in cell membrane fragility by anoxia." Pflugers Arch.416. 144-150 (1990)
[Publications] Inoue,M.et al.: "Inhibition of oxygen toxicity by trageting superoxide dismutase to endothelial cell surface." FEBS Lett.20. 89-92 (1990)
[Publications] Yoshida,A.et al.: "Molecular characterization of 1,4ーdihydropyridineーsensitive calcium channels of chick heart and skeletal muscle." J Biochem. 107. 608-612 (1990)
[Publications] Araki,H.et al.: "Effects of thrombosis on vascular tone in rat mesenteric arteries with endothelium in vivo." Circ Res.67. 312-318 (1990)
[Publications] Okazaki,O.et al.: "Modulation of Ca2+ transients and contractile properties by betaーadrenoceptor stimulation in ferret ventricular muscles." J Physiol. 423. 221-240 (1990)
[Publications] Goto,A.et al.: "Digitalisーlike activity in human plasma: relation to blood pressure and sodium balance." Am J Med.89. 420-426 (1990)
[Publications] Ohno,S.et al.: "A point mutation at the putative ATPーbinding site of site of protein kinase C alpha abolishes the kinase activity and renders it downーregulationーinsensitive.A molecular link between autophosphorylation and downーregulation." J Biol Chem.265. 6296-6300 (1990)
[Publications] Nishikawa,K.et al.: "Scavenger receptorーmediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages." J Biol Chem.265. 5226-5231 (1990)
[Publications] Suzuki,H.et al.: "Structure and regulation of rat longーchain acylーCoA synthetase." J Biol Chem.265. 8681-8685 (1990)
[Publications] Nishida,M.et al: "Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries." Circ Res.66. 253-258 (1990)
[Publications] Kuzuya T.et al: "Detection of oxygenーderived free radical generation in the canine postischemic heart during late phase of reperfusion." Circ Res.66. 1160-1165 (1990)
[Publications] Komuro,I.et al.: "Stretching cardiac myocytes stimulates protooncogene expression." J Biol Chem. 265. 3595-3598 (1990)
[Publications] Suzuki,H.et al.: "Common proteinーbinding sites in the 5'ーflanking regions of human geces for cytochrome cl and ubiquinoneーbinding protein." J Biol Chem. 265. 8159-8163 (1990)
[Publications] 多田道彦,中村隆雄他: "心臓の細胞生物学(蛋白核酸酵素増刊)" 共立出版,東京, 376 (1990)
[Publications] Tada,M.et al.: "Molecular Biology of the Myocardium" Japan Scientific Societies Press,Tokyo,

1990 Fiscal Year Annual Research Report

心筋細胞障害の成因と防御に関する基礎的研究

Principal Investigator

多田 道彦 大阪大学, 医学部, 教授 (90093434)

Research Products

[Publications] Katano,Y.et al.: "Differential effects of Ro 20ー1724 and isobutylmethylxanthine on the basal force of contraction and betaーadrenoceptorーmediated response in the rat ventricular myocardium." Biochem Biophys Res Commun. 167. 123-129 (1990)

[Publications] Matsubara,I.et al.: "Crossーbridge movement in rat cardiac muscle as a function of calcium concentration." J Physiol. 417. 555-565 (1999)

[Publications] Matsuoka,S.et al.: "Chlorideーsensitive nature of the adrenalineーinduced current in guineaーpig cardiac myocytes." J Physiol. 425. 579-598 (1990)

[Publications] Sugiura,H.et al.: "ATP directly affects junctional conductance between paired ventricular myocytes isolated from guinea pig heart." Circ Res.66. 1095-1102 (1990)

[Publications] Adaniya,H.et al.: "Effects of a novel class III antiarrhythmic agent,Eー4031,on reentrant tachycardias in rabbit right atrium." J Cardiovasc Pharmacol. 15. 976-982 (1990)

[Publications] Wakabayashi,S.et al.: "Mechanism for activation of the 4ーnitrobenzoー2ーoxaー1,3ーdiazoleーlabeled sarcoplasmic reticulum ATPase by Ca2+ and its modulation by nucleotides." Biochemistry. 29. 7309-7318 (1990)

[Publications] Iwai,K.et al.: "Disruption of microtubules as an early sign of irreversible ischemic injury.Immunohistochemical study of in situ canine hearts." Circ Res.67. 694-706 (1990)

[Publications] Kanatsuka,H.et al.: "Diameter change and pressureーred blood cell velocity relations in coronary microvessels during long diastoles in the canine left ventricle." Circ Res.66. 503-510 (1990)

[Publications] Fujitsuka,C.et al.: "Intramembrane particles and responses of sensory axon terminals during reinnervation of the frog muscle spindle." J Neurocytol. 19. 175-186 (1990)

[Publications] Hori,M.et al.: "An increase in myocardial betaーadrenoceptors to compensate for postischaemic dysfunction following coronary microーembolisation in dogs." Gardiovasc Res.23. 423-431 (1990)

[Publications] Tsutsui,H.et al.: "Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits." Circ Res.67. 368-375 (1990)

[Publications] Hamamori,Y.et al.: "5ーHydroxytryptamine induces phospholipase Cーmediated hydrolysis of phosphoinositides through 5ーhydroxytryptamineー2 receptors in cultured fetal mouse ventricular mvocvtes." Circ Res.66. 1474-1483 (1990)

[Publications] Ohta,Y et al.: "Ca2+/calmodulinーdependent protein kinase II:localization in the interphase nucleus and the mitotic apparatus of mammalian cells." Proc Natl Acad Sci USA. 87. 5341-5345 (1990)

[Publications] Hirooka,Y.et al.: "Attenuated forearm vasodilative response to intraーarterial atrial natriuretic peptide in patients with heart failure." Circulation. 82. 147-153 (1990)

[Publications] Komuro,I.et al.: "Molecular cloning of gene sequences from rat heart rapidly responsive to pressure overload." Circ Res.66. 979-985 (1990)

[Publications] Kotaka,M.et al.: "Experimental influenza A virus myocarditis in mice.Light and electron microscopic,virologic,and hemodynamic study." Am J Pathol. 136. 409-419 (1990)

[Publications] Koga,Y.et al.: "Decreased coronary vasodilatory capacity in hypertrophic cardiomyopathy determined by splitーdose thalliumーdipyridamole myocardial scintigraphy." Am J Cardiol. 65. 1134-1139 (1990)

[Publications] Ozawa,T.et al.: "Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy." Biochem Biophys Res Commun. 170. 830-836 (1990)

[Publications] Sato,H.et al.: "Acute hemodynamic effects of nilvadipine,a new calcium channel blocker,in patients with congestive heart failure." J Cardiovasc Pharmacol. 15. 317-322 (1990)

[Publications] Yamamoto,T.et al.: "Purification and characterization from bovine brain cytosol of proteins that regulate the GDP/GTP exchange reaction of smg p21s,ras p21ーlike GTPーbinding proteins." J Biol Chem.265. 16626-16634 (1990)

[Publications] Katori,M.et al.: "Evidence for the involvement of a plasma kallikreinーkinin system in the immediate hypotension produced by endotoxin in anaesthetized rats." Br J Pharmacol. 98. 1383-1391 (1990)

[Publications] Aoyama,T.et al.: "Prostaglandin I2 halfーlife regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris [see comments]." Circulation. 81. 1784-1791 (1990)

[Publications] Matsumoto,T.et al.: "Characteristics of the histamineーsensitive calcium store in vascular smooth muscle.Comparison with norepinephrineーor caffeineーsensitive stores." J Biol Chem. 265. 5610-5616 (1990)

[Publications] Fujita,H.et al: "A specific protein,p92,detected in flat revertants derived from NIH/3T3 transformed by human activated cーHaーras oncogene." Exp Cell Res.186. 115-121 (1990)

[Publications] Tona,L.et al.: "Depressant effects of chloroquine on the isolated guineaーpig heart." Eur J Pharmacol.178. 293-301 (1990)

[Publications] Kasanuki,H.et al.: "Differentiation and mechanisms of prevention and termination of verapamilーsensitive sustained ventricular tachvcardia." Am J Cardiol. 64. 46J-49J (1990)

[Publications] Yoshimoto,T.et al.: "Cloning and sequence analysis of the cDNA for arachidonate 12ーlipoxygenase of porcine leukocytes." Proc Natl Acad Sci USA. 87. 2142-2146 (1990)

[Publications] Nanto,S.et al.: "Percutaneous transluminal coronary angioplasty using kissing balloon technique in the left main trunk." Heart Vessels. 5. 107-112 (1990)

[Publications] Imaizumi,T.et al.: "Limited maximal vasodilator capacity of forearm resistance vessels in patients with hypertrophic cardiomyopathy." Heart Vessels.5. 159-165 (1990)

[Publications] Iijima,T.et al.: "Differential modulation by beta adrenoceptors of inward calcium and delayed rectifier potassium current in single ventricular cells of guinea pig heart." J Pharmacol Exp Ther. 254. 142-146 (1990)

[Publications] Kodama,I.et al.: "Two types of sodium channel block by classーI antiarrhythmic drugs studied by using Vmax of action potential in single ventricular myocytes." J Mol Cell Cardiol. 22. 1-12 (1990)

[Publications] Oike,M.et al: "Dual action of FRC8653,a novel dihydropyridine derivative,on the Ba2+ current recorded from the rabbit basilar artery." Circ Res. 67. 993-1006 (1990)

[Publications] Takuwa,Y.et al.: "Endothelin receptor is coupled to phospholipase C via a pertussis toxinーinsensitive guanine nucleotideーbinding regulatory protein in vascular smooth muscle cells." J Clin Invest. 85. 653-658 (1990)

[Publications] Kawaguchi,H.et al.: "Plateletーactivating factor stimulates angiotensin converting enzyme activity." J Hypertens. 8. 173-177 (1990)

[Publications] Okumura,K.et al.: "Norepinephrineーinduced 1,2ーdiacylglycerol accumulation and change in its fatty acid composition in the isolated perfused rat heart." Mol Cell Biochem. 93. 173-178 (1990)

[Publications] Nakamura,Y.et al.: "Comparative study of cell saver and ultrafiltration nontransfusion in cardiac surgery." Ann Thorac Surg. 49. 973-978 (1990)

[Publications] Takami,H.et al.: "Leakage of cytoplasmic enzymes from rat heart by the stress of cardiac beating after increase in cell membrane fragility by anoxia." Pflugers Arch.416. 144-150 (1990)

[Publications] Inoue,M.et al.: "Inhibition of oxygen toxicity by trageting superoxide dismutase to endothelial cell surface." FEBS Lett.20. 89-92 (1990)

[Publications] Yoshida,A.et al.: "Molecular characterization of 1,4ーdihydropyridineーsensitive calcium channels of chick heart and skeletal muscle." J Biochem. 107. 608-612 (1990)

[Publications] Araki,H.et al.: "Effects of thrombosis on vascular tone in rat mesenteric arteries with endothelium in vivo." Circ Res.67. 312-318 (1990)

[Publications] Okazaki,O.et al.: "Modulation of Ca2+ transients and contractile properties by betaーadrenoceptor stimulation in ferret ventricular muscles." J Physiol. 423. 221-240 (1990)

[Publications] Goto,A.et al.: "Digitalisーlike activity in human plasma: relation to blood pressure and sodium balance." Am J Med.89. 420-426 (1990)

[Publications] Ohno,S.et al.: "A point mutation at the putative ATPーbinding site of site of protein kinase C alpha abolishes the kinase activity and renders it downーregulationーinsensitive.A molecular link between autophosphorylation and downーregulation." J Biol Chem.265. 6296-6300 (1990)

[Publications] Nishikawa,K.et al.: "Scavenger receptorーmediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages." J Biol Chem.265. 5226-5231 (1990)

[Publications] Suzuki,H.et al.: "Structure and regulation of rat longーchain acylーCoA synthetase." J Biol Chem.265. 8681-8685 (1990)

[Publications] Nishida,M.et al: "Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries." Circ Res.66. 253-258 (1990)

[Publications] Kuzuya T.et al: "Detection of oxygenーderived free radical generation in the canine postischemic heart during late phase of reperfusion." Circ Res.66. 1160-1165 (1990)

[Publications] Komuro,I.et al.: "Stretching cardiac myocytes stimulates protooncogene expression." J Biol Chem. 265. 3595-3598 (1990)

[Publications] Suzuki,H.et al.: "Common proteinーbinding sites in the 5'ーflanking regions of human geces for cytochrome cl and ubiquinoneーbinding protein." J Biol Chem. 265. 8159-8163 (1990)

[Publications] 多田 道彦,中村 隆雄 他: "心臓の細胞生物学(蛋白核酸酵素増刊)" 共立出版,東京, 376 (1990)

[Publications] Tada,M.et al.: "Molecular Biology of the Myocardium" Japan Scientific Societies Press,Tokyo,

多田道彦大阪大学, 医学部, 教授 (90093434)

[Publications] 多田道彦,中村隆雄他: "心臓の細胞生物学(蛋白核酸酵素増刊)" 共立出版,東京, 376 (1990)