心筋細胞障害の成因と防御に関する基礎的研究

• 研究課題/領域番号: 02299111
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 大阪大学
• 研究代表者: 多田 道彦 大阪大学, 医学部, 教授 (90093434)
• 研究分担者: 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)
• 研究期間 (年度): 1990
• 研究課題ステータス: 完了 (1990年度)
• 配分額: 3,000千円 (直接経費: 3,000千円); 1990年度: 3,000千円 (直接経費: 3,000千円)
• キーワード: 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

研究概要

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。

研究成果

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