1989 年度実績報告書

酸化還元エネルギー

研究課題

研究課題/領域番号	01617002
研究機関	名古屋大学
研究代表者	小澤高将名古屋大学, 医学部, 教授 (80022771)
研究分担者	小池正彦長崎大学, 医学部, 教授 (10039521) 松原央大阪大学, 理学部, 教授 (00028242) 多田啓也東北大学, 医学部, 教授 (20046907) 佐藤猛順天堂大学, 医学部, 助教授 (40018594) 折井豊京都大学, 医学部, 助教授 (60028149)
キーワード	ミトコンドリアDNA / 遺伝子欠失 / チトクロムc_1遺伝子 / ピルビン酸脱水酵素遺伝子 / レーバー氏病 / 特発性心筋症 / チトクロムc酸化酵素 / 労作性ミオグロビン尿症
研究概要	小澤らはミトコンドリア(mt)DNA多重欠失を発見し、欠失発生への直接繰返し配列の関与を示した。また核DNAの協調的発現に係わる塩基配列を解明した。折井は、チトクロム酸化酵素の反応中間体であるperoxy型とferryl型を灌流肝臓で検出し反応機構の普遍性を確認した。佐藤は23例の例のmtミオパチーと11例の他疾患の生検筋のmtのサザンブロット解析を行い、10例のmtミオパチーにmtDNAの欠失を認めた。5例の筋についてin situ hybridizationを行い、欠失mtDNAの分布を明らかにした。多田は、mt脳筋症47例のサザン法により検討し、mtDNAのdeletionを5例に認めた。1例は眼筋ミオパチーであったが、他の4例は、臨床的に眼筋麻痺やRRFを認めず、欠失mtDNAの割合が低い点が特異であった。松原はユーグレナ・チトクロムc_1のcDNAの塩基配列を決定した。システィン39が唯一のヘム結合残基であること、ヘム鉄の配位子がヒスチジン44とメチオニン164とであることを明らかにした。小池は、ピルビン酸脱水素酵素(PDH)α、β遺伝子の単離と全構造解析を行い、両遺伝子の発現機序を解明し、ATP産生応答における本酵素の役割を明らかにした。埜中は、mtミオパチーにおけるチトクロムc酸化酵素欠損は1本の筋線維内にも節状に分布するものと、分節が不明瞭なものの二群があることを明らかにした。宝来はヒトmtDNAのDループ領域の塩基配列を3大人種よりなる95人について決定し、系統樹を作成した。戸嶋はヒト心筋症心筋生検組織について電子伝達系酵素複合体に対する抗体を用いた免疫組織化学研究を行い、染色性低下を肥大型、拡張型心筋症の一部において証明した。宮武はLeber氏病においてmtDNAに点塩基変異の存在することを日本人において初めて見出した。佐橋はまた再発性ミオグロビン尿兄弟症例においてmtDNAの多重欠失を証明した。本研究によりmt遺伝子の発現機構およびその異常の広範な疾患への関与が明確にされた。

研究成果

(46件)

すべてその他

すべて文献書誌 (46件)

[文献書誌] H.Suzuki: "Structural Organization of the Human Mitochondrial Cytochrome c1 Gene" J.Biol.Chem.264. 1368-1374 (1989)
[文献書誌] T.Ichiki: "Disproportionate Deficiency of Iron-Sulfur Clusters and Subunits of Complex I in Mitochondrial Encephalomyopathy(MELAS)" Pediatr.Res.25. 194-201 (1989)
[文献書誌] M.Nishikimi: "Cloning and Sequence Analysis of a cDNA Encoding the Rieske Iron-sulfur Protein of Rat Mitochondrial Cytochrome bc1" Biochem.Biophys.Res.Commun.159. 19-25 (1989)
[文献書誌] A.W.Linnane: "Mitochondrial DNA Mutations as an Important Contributor to Aging and Degenerative Diseases" Lancet. i. 642-645 (1989)
[文献書誌] M.Yoneda: "A Maternally Inherited Mitochondrial DNA Mutation in a Japanese Family with Leber′s Hereditary Optic Neuropathy." Lancet. i. 1076-1077 (1989)
[文献書誌] K.Seki: "Decreased Activity of Cytochrome c Oxidase in the Macular Mottled Mouse: anImmuno-Electron Microscopc Study" Acta Neuropathol.17. 465-471 (1989)
[文献書誌] M.Tanaka: "Direct Sequencing of Deleted Mitochondrial DNA in Myopathic Patients" Biochem.Biophys.Res.Commun.164. 156-163 (1989)
[文献書誌] T.Tanaka-Yamamoto: "Specific Amplification of Deleted Mitochondrial DNA from a Myopathic Patient and Analysis of Deleted Region with S1 Nuclease." Biochim.Biophys.Acta. 1009. 151-155 (1989)
[文献書誌] H.Toda: "Cloning and Sequencing of a cDNA Encoding the Precursor to the 24-kDa Iron-Sulfur Protein of Human Mitochondrial NADH Dehydrogenase" Int.J.Biochem.21. 1161-1168 (1989)
[文献書誌] M.Nishikimi: "The Primary Structure of Human Rieske Iron-sulfur Protein of Mitochondrial Cytochrome bcl Complex Deduced from cDNA Analysis." Biochem.Int.20. 155-160 (1989)
[文献書誌] T.Ito: "Mitochondrial Cytopathy" Jpn.Circ J.(1989)
[文献書誌] K.Jinnai: "A Case of Mitochondrial Myopathy,Encephalopathy,and Lactic Acidosis(MELA)due to Cytochrome c Oxidase Dificiency with Neurogenic Muscular Changes" Eur.J.Neurol.(1989)
[文献書誌] H.Suzuki: "Isolation of a Single Nuclear Gene Encoding Human Ubiquinone-Binding Protein in Complex III of Mitochondrial Respiratory Chain." Biochem.Biophys.Res.Commun.161. 371-378 (1989)
[文献書誌] W.Sato: "Multiple Populations of Deleted Mitochondrial DNA Detected by a Novel Gene Amplification Method" Biochem.Biophys.Res.Commun. 162. 664-672 (1989)
[文献書誌] Y.Hosokawa: "Complementary DNA Encoding Core Protein II of Human Mitochondrial Cytochrome bcl Complex.Substantial Diversity in Deduced Primary Structure from its Yeast Counterpart" J.Biol.Chem.264. 13483-13488 (1989)
[文献書誌] M.Yoneda: "Pleiotropic Molecular Defects in Energy-transducing Complexes in Mitochondrial Encephalomyopathy(MELAS)" J.Neurol.Sci.92. 143-158 (1989)
[文献書誌] M.Tanaka: "Differently Deleted Mitochondrial Genomes in Maternally Inherited Chronic Progressive External Ophthalmoplegia." J.Inher.Metab.Dis.12. 359-362 (1989)
[文献書誌] Y.Mizuno: "Deficiencies in Complex I Subunits of the Respiratory Chain in Parkinson′s Disease" Biochem.Biophys.Res.Commun. 163;3. 1450-1455 (1989)
[文献書誌] K.Sevama: "Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes with Special Reference to the Mechanism of Cerebral Manifestations." Acta Neurol.Scan.(1989)
[文献書誌] Y.Koga: "Multisystemic Cytochrome c Oxidase Deficiency with Clinical Characteristics of Leigh′s Disease." J.Neurol.Sci.(1989)
[文献書誌] Y.Hosokawa: "The Primary Structure of The precursor to Core Protein II,a Putative Member of Mitochondrial Processing Protease Family,of Rat Mitochondrial Cytochrome bcl complex Deduced From cDNA Sequence Analysis" Biochem.Int.(1989)
[文献書誌] Yutaka Orii: "UBIQUTTOUS FORMATION OF CATALASE COMPOUND II IN HEMOGLOBIN FREE PERFUSED RAT LIVER AND DETECTION OF NAVEL SPECTRAL SPECIES" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 162. 1272-1278 (1989)
[文献書誌] S.YOSHIDA: "SPECIFIC INHIBITION OF THE REDOXーLINKED PROTON PUMP ACTIVITY OF CYTOCHROME OXIDASE BY OLEATE HYDROPEROXIDE AND INVOLVEMENT OF FERROCYTOCHROME C IN THE HYDROPEROXIDE CATABOLISM" Biochem.Int.
[文献書誌] 折井豊: "へムタンパクの光化学反応" 生物物理. 29. S200 (1989)
[文献書誌] 折井豊: "チトクロム酸化酵素の機能に関連した新しい型の阻害様式" 生化学. 61. 1133 (1989)
[文献書誌] Sato T.: "Mitochondrial myopathies:Morphological approach to molecular abnormalities" Bioenergitics:Molecular biology,biochemistry and pathology,eds Kim CH and Ozawa T. (1989)
[文献書誌] Sato T.: "Defect in cytochrome c oxidase messenger RNA in chronic external ophthalmoplegia:Detection by in situ hybridization" Annals of Neurology. 26. 145-146 (1989)
[文献書誌] Seki K.: "Decreased activity of cytochrome c oxidase in the macular mottled mice:an immuno-electron microscopic study" Acta Neuropathologica. 77. 456-471 (1989)
[文献書誌] Ihara Y.: "Mitochondrial encephalomyopathy(MELAS):Pathological study and successful therapy with coenzyme Q10 and idebenone" J Neurological Science. 90. 263-271 (1989)
[文献書誌] Nakamura S.: "In situ hybridization of muscle mitochondrial mRNA in mitochondrial myopathies" Acta Neuropathologica. (1990)
[文献書誌] 宋東林: "全コロイド標識免疫電子顕微鏡によるミトコンドリアミオパチーの研究" 臨床神経学. 29. 405-410 (1989)
[文献書誌] S.Miyabayashi: "Defective pattern of mitochondrial respiratory eszymes in mitochondrial myopathy" J.Inher.Metab.Dis.12. 373-377 (1989)
[文献書誌] K.Haginoya: "Electron cytochemistry of cytochrome c oxidase in biopsied muscle of the patients with cytochrome c oxidase deficiency and related mitochondrial myopathy." Acta Neuropathologica.
[文献書誌] C.C.Su: "Familial MELAS(mitochondrial myopathy,encephalopathy,lactic,acidosis and stroke-like episodes)with cytochrome b deficiency" Neuroradiology.
[文献書誌] 宮林重明: "ミトコンドリア病" 脳性麻痺.
[文献書誌] K.Mukai: "An Atypical Heme-Binding Structure of Cytochrome C__ー_1 of Euglena gracilis Mitochondrial Complex III" Eur.J.Biochem.178. 649-656 (1989)
[文献書誌] M.Nakai: "Protein Sorting between Outer and Inner Mitochondrial Membrancs:Submitochondrial Localization of Cytochrome C__ー_1 Whose Presequence is Replaced by the AminoーTerminal Region of a 70 kDa Outer Membrane Protein" J.Biochem.106. 181-187 (1989)
[文献書誌] 向井邦晃: "Euglenaミトコンドリアの呼吸鎖電子伝達系ーシトクロムbc_1複合体の比較生化学" 日本農芸化学会誌. 63. 1509-1512 (1989)
[文献書誌] K.Mukai: "Molecular Cloning and Nucleotide Sequence of a cDNA Encoding Englena gracilis Cytochrome C__ー_1" J.Biochem.106. 479-482 (1989)
[文献書誌] H.Matsubara: "Structural Studies of Euglena Cytocrome C__ー_1" Bioenergetics-Moleculer Biology,Biochemistry and Pathology. Proceeding. (1990)
[文献書誌] Kichiko Koike: "Molecular Cloning of cDNAs for α and β Subunits of Human Pyruvate Dehydrogenase" Annals New York Academy of Sciences. 573. 100-112 (1989)
[文献書誌] Yoshishige Urata: "Chronic Acidemia Due to a Pyruvate Dehydrogenase Deficiency in pyruvate Dehydrogenase Complex,with Abnormalities of the α and β Subunits of the Enzyme" Annals New York Academy of Sciences. 573. 450-452 (1989)
[文献書誌] 小池吉子: "ヒトピルビン酸脱水素酵素αサブユニット遺伝子の単離と構造解析" 生化学. 61. 842 (1989)
[文献書誌] 浦田芳重: "原発性胆汁性肝硬変症の自己抗原一次構造解析と簡易診断法の開発" 生化学. 61. 914 (1989)
[文献書誌] 浦田芳重: "ヒトピルビン酸脱水素酵素αサブユニットの一次構造の比較生化学" 生化学. 61. 1139 (1989)
[文献書誌] Yutaka Orii: "Bioenergetics:Molecular Biology,Biochemistry,and Pathology" CYTOCHROME OXIDASE AND PEROXIDE METABOLISM,

1989 年度 実績報告書

酸化還元エネルギー

研究代表者

小澤 高将 名古屋大学, 医学部, 教授 (80022771)

研究成果

[文献書誌] H.Suzuki: "Structural Organization of the Human Mitochondrial Cytochrome c1 Gene" J.Biol.Chem.264. 1368-1374 (1989)

[文献書誌] T.Ichiki: "Disproportionate Deficiency of Iron-Sulfur Clusters and Subunits of Complex I in Mitochondrial Encephalomyopathy(MELAS)" Pediatr.Res.25. 194-201 (1989)

[文献書誌] M.Nishikimi: "Cloning and Sequence Analysis of a cDNA Encoding the Rieske Iron-sulfur Protein of Rat Mitochondrial Cytochrome bc1" Biochem.Biophys.Res.Commun.159. 19-25 (1989)

[文献書誌] A.W.Linnane: "Mitochondrial DNA Mutations as an Important Contributor to Aging and Degenerative Diseases" Lancet. i. 642-645 (1989)

[文献書誌] M.Yoneda: "A Maternally Inherited Mitochondrial DNA Mutation in a Japanese Family with Leber′s Hereditary Optic Neuropathy." Lancet. i. 1076-1077 (1989)

[文献書誌] K.Seki: "Decreased Activity of Cytochrome c Oxidase in the Macular Mottled Mouse: anImmuno-Electron Microscopc Study" Acta Neuropathol.17. 465-471 (1989)

[文献書誌] M.Tanaka: "Direct Sequencing of Deleted Mitochondrial DNA in Myopathic Patients" Biochem.Biophys.Res.Commun.164. 156-163 (1989)

[文献書誌] T.Tanaka-Yamamoto: "Specific Amplification of Deleted Mitochondrial DNA from a Myopathic Patient and Analysis of Deleted Region with S1 Nuclease." Biochim.Biophys.Acta. 1009. 151-155 (1989)

[文献書誌] H.Toda: "Cloning and Sequencing of a cDNA Encoding the Precursor to the 24-kDa Iron-Sulfur Protein of Human Mitochondrial NADH Dehydrogenase" Int.J.Biochem.21. 1161-1168 (1989)

[文献書誌] M.Nishikimi: "The Primary Structure of Human Rieske Iron-sulfur Protein of Mitochondrial Cytochrome bcl Complex Deduced from cDNA Analysis." Biochem.Int.20. 155-160 (1989)

[文献書誌] T.Ito: "Mitochondrial Cytopathy" Jpn.Circ J.(1989)

[文献書誌] K.Jinnai: "A Case of Mitochondrial Myopathy,Encephalopathy,and Lactic Acidosis(MELA)due to Cytochrome c Oxidase Dificiency with Neurogenic Muscular Changes" Eur.J.Neurol.(1989)

[文献書誌] H.Suzuki: "Isolation of a Single Nuclear Gene Encoding Human Ubiquinone-Binding Protein in Complex III of Mitochondrial Respiratory Chain." Biochem.Biophys.Res.Commun.161. 371-378 (1989)

[文献書誌] W.Sato: "Multiple Populations of Deleted Mitochondrial DNA Detected by a Novel Gene Amplification Method" Biochem.Biophys.Res.Commun. 162. 664-672 (1989)

[文献書誌] Y.Hosokawa: "Complementary DNA Encoding Core Protein II of Human Mitochondrial Cytochrome bcl Complex.Substantial Diversity in Deduced Primary Structure from its Yeast Counterpart" J.Biol.Chem.264. 13483-13488 (1989)

[文献書誌] M.Yoneda: "Pleiotropic Molecular Defects in Energy-transducing Complexes in Mitochondrial Encephalomyopathy(MELAS)" J.Neurol.Sci.92. 143-158 (1989)

[文献書誌] M.Tanaka: "Differently Deleted Mitochondrial Genomes in Maternally Inherited Chronic Progressive External Ophthalmoplegia." J.Inher.Metab.Dis.12. 359-362 (1989)

[文献書誌] Y.Mizuno: "Deficiencies in Complex I Subunits of the Respiratory Chain in Parkinson′s Disease" Biochem.Biophys.Res.Commun. 163;3. 1450-1455 (1989)

[文献書誌] K.Sevama: "Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes with Special Reference to the Mechanism of Cerebral Manifestations." Acta Neurol.Scan.(1989)

[文献書誌] Y.Koga: "Multisystemic Cytochrome c Oxidase Deficiency with Clinical Characteristics of Leigh′s Disease." J.Neurol.Sci.(1989)

[文献書誌] Y.Hosokawa: "The Primary Structure of The precursor to Core Protein II,a Putative Member of Mitochondrial Processing Protease Family,of Rat Mitochondrial Cytochrome bcl complex Deduced From cDNA Sequence Analysis" Biochem.Int.(1989)

[文献書誌] Yutaka Orii: "UBIQUTTOUS FORMATION OF CATALASE COMPOUND II IN HEMOGLOBIN FREE PERFUSED RAT LIVER AND DETECTION OF NAVEL SPECTRAL SPECIES" BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 162. 1272-1278 (1989)

[文献書誌] S.YOSHIDA: "SPECIFIC INHIBITION OF THE REDOXーLINKED PROTON PUMP ACTIVITY OF CYTOCHROME OXIDASE BY OLEATE HYDROPEROXIDE AND INVOLVEMENT OF FERROCYTOCHROME C IN THE HYDROPEROXIDE CATABOLISM" Biochem.Int.

[文献書誌] 折井豊: "へムタンパクの光化学反応" 生物物理. 29. S200 (1989)

[文献書誌] 折井豊: "チトクロム酸化酵素の機能に関連した新しい型の阻害様式" 生化学. 61. 1133 (1989)

[文献書誌] Sato T.: "Mitochondrial myopathies:Morphological approach to molecular abnormalities" Bioenergitics:Molecular biology,biochemistry and pathology,eds Kim CH and Ozawa T. (1989)

[文献書誌] Sato T.: "Defect in cytochrome c oxidase messenger RNA in chronic external ophthalmoplegia:Detection by in situ hybridization" Annals of Neurology. 26. 145-146 (1989)

[文献書誌] Seki K.: "Decreased activity of cytochrome c oxidase in the macular mottled mice:an immuno-electron microscopic study" Acta Neuropathologica. 77. 456-471 (1989)

[文献書誌] Ihara Y.: "Mitochondrial encephalomyopathy(MELAS):Pathological study and successful therapy with coenzyme Q10 and idebenone" J Neurological Science. 90. 263-271 (1989)

[文献書誌] Nakamura S.: "In situ hybridization of muscle mitochondrial mRNA in mitochondrial myopathies" Acta Neuropathologica. (1990)

[文献書誌] 宋東林: "全コロイド標識免疫電子顕微鏡によるミトコンドリアミオパチーの研究" 臨床神経学. 29. 405-410 (1989)

[文献書誌] S.Miyabayashi: "Defective pattern of mitochondrial respiratory eszymes in mitochondrial myopathy" J.Inher.Metab.Dis.12. 373-377 (1989)

[文献書誌] K.Haginoya: "Electron cytochemistry of cytochrome c oxidase in biopsied muscle of the patients with cytochrome c oxidase deficiency and related mitochondrial myopathy." Acta Neuropathologica.

[文献書誌] C.C.Su: "Familial MELAS(mitochondrial myopathy,encephalopathy,lactic,acidosis and stroke-like episodes)with cytochrome b deficiency" Neuroradiology.

[文献書誌] 宮林重明: "ミトコンドリア病" 脳性麻痺.

[文献書誌] K.Mukai: "An Atypical Heme-Binding Structure of Cytochrome C__ー_1 of Euglena gracilis Mitochondrial Complex III" Eur.J.Biochem.178. 649-656 (1989)

[文献書誌] M.Nakai: "Protein Sorting between Outer and Inner Mitochondrial Membrancs:Submitochondrial Localization of Cytochrome C__ー_1 Whose Presequence is Replaced by the AminoーTerminal Region of a 70 kDa Outer Membrane Protein" J.Biochem.106. 181-187 (1989)

[文献書誌] 向井邦晃: "Euglenaミトコンドリアの呼吸鎖電子伝達系ーシトクロムbc_1複合体の比較生化学" 日本農芸化学会誌. 63. 1509-1512 (1989)

[文献書誌] K.Mukai: "Molecular Cloning and Nucleotide Sequence of a cDNA Encoding Englena gracilis Cytochrome C__ー_1" J.Biochem.106. 479-482 (1989)

[文献書誌] H.Matsubara: "Structural Studies of Euglena Cytocrome C__ー_1" Bioenergetics-Moleculer Biology,Biochemistry and Pathology. Proceeding. (1990)

[文献書誌] Kichiko Koike: "Molecular Cloning of cDNAs for α and β Subunits of Human Pyruvate Dehydrogenase" Annals New York Academy of Sciences. 573. 100-112 (1989)

[文献書誌] Yoshishige Urata: "Chronic Acidemia Due to a Pyruvate Dehydrogenase Deficiency in pyruvate Dehydrogenase Complex,with Abnormalities of the α and β Subunits of the Enzyme" Annals New York Academy of Sciences. 573. 450-452 (1989)

[文献書誌] 小池吉子: "ヒトピルビン酸脱水素酵素αサブユニット遺伝子の単離と構造解析" 生化学. 61. 842 (1989)

[文献書誌] 浦田芳重: "原発性胆汁性肝硬変症の自己抗原一次構造解析と簡易診断法の開発" 生化学. 61. 914 (1989)

[文献書誌] 浦田芳重: "ヒトピルビン酸脱水素酵素αサブユニットの一次構造の比較生化学" 生化学. 61. 1139 (1989)

[文献書誌] Yutaka Orii: "Bioenergetics:Molecular Biology,Biochemistry,and Pathology" CYTOCHROME OXIDASE AND PEROXIDE METABOLISM,

1989 年度実績報告書

小澤高将名古屋大学, 医学部, 教授 (80022771)