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老年病および生活習慣病におけるミトコンドリアからの活性酸素の放出機構

Research Project

Project/Area Number 06F06458
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field General medical chemistry
Research InstitutionNippon Medical School

Principal Investigator

太田 成男  Nippon Medical School, 大学院・医学研究科, 教授 (00125832)

Co-Investigator(Kenkyū-buntansha) MARTIN Wolf Alexander  日本医科大学, 老人病研究所生化学部門, 外国人特別研究員
WOLF Alexander Martin  日本医科大学, 老人病研究所, 外国人特別研究員
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2008: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2007: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Keywordsミトコンドリア / 老年病 / 活性酸素
Research Abstract

本研究の目的はミトコンドリアから発せられる活性酸素量とミトコンドリア膜電位およびマトリックス内のカルシウム濃度など他のミトコンドリア特性を同時に測定する事にあった。測定方法として多数の蛍光色素また蛍光蛋白はを試した結果、測定に一番有効な方法はミトコンドリア内に酸化還元状態によって蛍光が変化するroGFP(蛍光蛋白質)を発現させる事であった。ミトコンドリアの活性酸素の発生によって変わるミトコンドリア内の酸化還元状態をroGFPによって生きた細胞内で測定し、ミトコンドリア膜電位を減少させるによってミトコンドリアの活性酸素発生量が減少する事を証明した。このメカニズムは単離ミトコンドリアて良く知られているが、今回、生きた細胞内でミトコンドリア特異的測定をすることに初めて成功した。この結果をThe 15th European Bioenergetics Conference 2008で発表し現在論文を作成している。
更にroGFPを用いてカロテノイド系色素物質であるアスタキサンチンが生理的な濃度でミトコンドリア内の酸化還元状態を酸化ストレスに対して還元状態に保つ事ができ、その事によってミトコンドリア膜電位やミトコンドリア酸素消費等ミトコンドリア機能を保護しアスタキサンチンが酸化ストレスに対して高い抗酸化作用を持つ事を証明できた。この結果の論文をJournal of Nutritional Biochemistryに投稿し受理された。

Report

(3 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (33 results)

All 2009 2008 2007 2006 Other

All Journal Article (21 results) (of which Peer Reviewed: 13 results) Presentation (9 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease2009

    • Author(s)
      Fu Y, et al.
    • Journal Title

      Neurosci. Letters (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice2009

    • Author(s)
      Nakashima-Kamimura N, et al.
    • Journal Title

      Cancer Chemother Phrmacol. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice2009

    • Author(s)
      Nagata K, et al.
    • Journal Title

      Neuropsychopharmacology 34

      Pages: 501-508

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice2008

    • Author(s)
      Ohsawa I, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 377

      Pages: 1195-1198

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model2008

    • Author(s)
      Cai J, et al.
    • Journal Title

      Neurosci Lett. 441

      Pages: 167-172

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury2008

    • Author(s)
      Hayashida K., et al.
    • Journal Title

      Biochem Biophys Res Commun. 373

      Pages: 30-35

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imaging mitochondrial redox environment and oxidative stress using a redox-sensitive fluorescent protein2008

    • Author(s)
      Wolf AM, et al.
    • Journal Title

      J Nippon Med Sch 75

      Pages: 66-67

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.2007

    • Author(s)
      Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K-I, Katayama Y, Asoh S, Ohta S
    • Journal Title

      Nat. Med. 13

      Pages: 688-694

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress.2007

    • Author(s)
      Fukuda KI, Asoh S, Ishikawa M, Yamamoto Y, Ohta S.
    • Journal Title

      Biochem. Biophys. Res. Commun. 361

      Pages: 670-674

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transduction of anti-cell death protein FNK protects isolated rat hearts from myocardial infarction induced by ischemia/reperfusion.2007

    • Author(s)
      Arakawa M, Yasutake M, Asoh S, Miyamoto M, Takano T, Ohta S.
    • Journal Title

      Life Sci. 80

      Pages: 2076-2084

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Protein Derived From the Fusion of TAT Peptide and FNK, a Bcl-X_L Derivative, prevents Cochlear Hair Cell Death From Aminoglycoside Ototoxicity In Vivo2007

    • Author(s)
      Kashio A, Sakamoto T, Suzukawa K, Asoh S, Ohta S, Yamasoba T.
    • Journal Title

      J Neurosci. Res. 85

      Pages: 1403-1412

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of Chemotherapy-Induced Alopecia by anti-death FNK protein.2007

    • Author(s)
      Nakashima-Kamimura N, Nishimaki K, Mori T, Asoh S, Ohta S.
    • Journal Title

      Life Sci. 82

      Pages: 218-225

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-apoptotic PTD-FNK protein suppresses lipopolysaccharide-inducedacute lung injury in rats Experimental and Molecular Pathology2007

    • Author(s)
      Chen H, Zhang L, Jin Z, Jin E, Fujiwara M, Ghazizadeh M, Asoh S, Ohta S, Kawanami O.
    • Journal Title

      Exp. Mol. Pathol. 83

      Pages: 377-384

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transduction of the anti-apoptotic PTD-FNK protein improves the efficiency of transplantation of bone marrow mononuclear cells.2007

    • Author(s)
      Tata S., Miyamoto M., Asoh S., Ishii N., Yasutake M., Takagi G., Takano T., Ohta S.
    • Journal Title

      J. Mol. Cell Cardiol. 42・3

      Pages: 489-497

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protection of hepatic cells from apoptosis induced by ischemia/reperfusion injury by protein therapeutics.2007

    • Author(s)
      Nagai S., Asoh S., Kobayashi Y., Shidata Y., Mori T., Suzuki M., Moriyama Y., Ohta S.
    • Journal Title

      Hepatol. Res. 37・2

      Pages: 133-142

    • NAID

      10018567444

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Contribution of somatic mutations in the mitochondrial genome to the development of cancer and tolerance against anticancer drugs.2006

    • Author(s)
      Ohta S.
    • Journal Title

      Oncogene 25・34

      Pages: 4768-4776

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dysfunction of mitochondria and oxidative stress in pathogenesis of Alzheimer's disease : On defects in the cytochrome c oxidase complex and aldehyde detoxification.2006

    • Author(s)
      Ohta S., Ohsawa I.
    • Journal Title

      J. Alzheimer's Disease 9・2

      Pages: 155-166

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese.2006

    • Author(s)
      Suzuki Y., Ando F., Ohsawa I., Shimokata H., Ohta S.
    • Journal Title

      J. Hum. Genet. 51・1

      Pages: 31-37

    • NAID

      10020558185

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hydrogen acts as a therapeutic antioxidant by the selective reduction of cytotoxic oxygen radicals.

    • Author(s)
      Ohsawa I., Ishikawa M., Takahashi K., Watanabe M., Nishimaki K., Yamagata K., Katsura K.-I., Katayama Y., Asoh S., Ohta S.
    • Journal Title

      Nat. Med. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transduction of anti-cell death protein FNK protects isolated rat hearts from myocardial infarction induced by ischemia/reperfusion.

    • Author(s)
      Arakawa M., Yasutake M., Asoh S., Miyamoto M., Takano T., Ohta S.
    • Journal Title

      Life Sci. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A Protein Derived From the Fusion of TAT Peptide and FNK, <a Bcl-X_L> Derivative, prevents Cochlear Hair Cell Death From Aminoglyooside Ototoxicity In Vivo.

    • Author(s)
      Kashio A., Sakamoto T., Suzukawa K., Asoh S., Ohta S., Yamasoba T.
    • Journal Title

      J. Neurosci. Res. (in press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] 水素水の基礎と臨床応用の可能性2009

    • Author(s)
      太田成男
    • Organizer
      日本抗加齢学会
    • Place of Presentation
      東京
    • Year and Date
      2009-01-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mild uncoupling が生細胞内の酸化ストレスを減少させる2008

    • Author(s)
      Wolf, AM., et al.
    • Organizer
      第8回日本ミトコンドリア学会年会
    • Place of Presentation
      東京
    • Year and Date
      2008-12-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mild uncoupling reduces oxidative stress in intact cells2008

    • Author(s)
      Wolf, AM., et al.
    • Organizer
      BMB2008第31回日本分子生物学会/第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mild uncoupling reduces oxidative stress in intact cells2008

    • Author(s)
      Wolf Alexander Martin
    • Organizer
      The 15th European Bioenergetics Conference 2008
    • Place of Presentation
      Ireland Dublin
    • Year and Date
      2008-07-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] Hydrogen acts as a therapeutic and preventive antioxidant2008

    • Author(s)
      Ohta S.
    • Organizer
      The_seventh European Meeting on Mitochondrial Pathology
    • Place of Presentation
      Sweden Stockholm
    • Year and Date
      2008-06-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] 水素の抗酸化治療への適応と将来展望・・水素ガスおよび水素水の広がる期待2007

    • Author(s)
      太田 成男
    • Organizer
      第7回日本マイナスイオン応用学会
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] 抗酸化療法:水素は細胞障害性酸化ラジカルを選択的に還元することで治療に有効な抗酸化剤として作用する。2007

    • Author(s)
      太田 成男
    • Organizer
      世界アンチエイジング日本会議
    • Place of Presentation
      東京
    • Year and Date
      2007-06-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] An Efficient Antioxidant by Molecular Hydrogen as a Novel Concept.2007

    • Author(s)
      Shigeo Ohta
    • Organizer
      15th Annual world congress on anti-aging medicine & regenerative biomedical technologies
    • Place of Presentation
      USA Las Vegas
    • Related Report
      2007 Annual Research Report
  • [Presentation] ミトコンドリア内の酸化還元状態の測定・・・アスタキサンチンは酸化ストレスに対してミトコンドリア内を還元状態に向かわせる。2007

    • Author(s)
      Wolf, Alexander, M.
    • Organizer
      第6回日本ミトコンドリア学会
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Book] ミトコンドリアのちから2007

    • Author(s)
      瀬名秀明・太田成男
    • Total Pages
      423
    • Publisher
      新潮社
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.ig.nms.ac.jp/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.nms.ac.jp/ig/biocell/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2024-03-26  

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