Analysis of mitochondrial dysfunction on Familial Amyotrophic lateral Sclerosis and The development of new cure

• Project/Area Number: 18790227
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Osaka City University
• Principal Investigator: KIRA Yukimi Osaka City University, 医学部, 技術職員 (90420728)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: 筋萎縮性側索硬化症 / ミトコンドリア / カルニチン / 酸化障害 / 治療

Research Abstract

神経系や骨格筋のようなミトコンドリア依存性の高い組織では、正常なミトコンドリア機能の維持がきわめて重要である。研究代表者はミトコンドリアに注目した解析により、FALS の病態発症のメカニズムと新規治療法の開発に取り組み、研究期間内に以下のことを明らかにした。
(1)細胞質局在だと言われていたSOD1(Cu/Zn-SOD1)はミトコンドリアに可逆的に結合局在し、ミトコンドリアの機能とその局在に相関関係がある。
(2)家族性筋萎縮性側索硬化症モデルマウス(FALS Tg)を用いた解析の結果、FALSでは病態の発症及び進行にミトコンドリアの機能障害が関与している。
(3)ミトコンドリア保護作用のあるカルニチンはFALS Tgの病態発症遅延効果と延命効果がある。

Research Products

• [Journal Article] The identification and Characterization of a new GTP-binding protein (Gbp45) involved in cell proliferation and death related to mitochondrial function (2008)
  • Author(s): Kira Y, Nishikawa
  • Journal Title: Cellular & Molecular Biology Letters 13 Pages: 570-580
  • Peer Reviewed
• [Journal Article] Prevention of venous thrombosis by preoperative glycyrrhizin infusion in a rat model (2008)
  • Author(s): Nakata N, Kira Y, Yabunaka Y, Takaoka K. J Orthop
  • Journal Title: Journal of orthopaedic science 13 Pages: 456-462
  • NAID: 10024301725
  • Peer Reviewed
• [Journal Article] Effect of CoQ homologues on reactive oxygen generation by mitochondria (2008)
  • Author(s): Imada I, Sato EF, Kira Y, Inoue M
  • Journal Title: Biofactors 32 Pages: 41-48
  • Peer Reviewed
• [Journal Article] The identification and Characterization of a new GTPbinding protein (Gbp45) involved in cell nroliferation and death related to mitochondrial function (2008)
  • Author(s): Kira Y, Nishikawa
  • Journal Title: Cellular & Molecular Biology Letters 13 Pages: 570-580
  • Peer Reviewed
• [Journal Article] Effect of CoQ homologues on reactive oxygen generation by mitochondria (2008)
  • Author(s): Imada I, Sato EF, Kira Y, Inoue M.
  • Journal Title: Biofactors 32 Pages: 41-48
  • Peer Reviewed
• [Journal Article] Prevention of venous thrombosis by preoperative glycyn-hizin infusion in a rat model (2008)
  • Author(s): Nakata N, Kira Y, Yabunaka Y, Takaoka K. J Orthop
  • Journal Title: Journal of orthopaedic science 13 Pages: 456-462
  • Peer Reviewed
• [Journal Article] Identification and Characterization of a GTP-binding protein with molecular weight of 45 kD:Gbp45 (2008)
  • Author(s): Kira Y and Nishikawa M
  • Journal Title: Cellular&Molecular Biology Letters (in press)
  • Peer Reviewed
• [Journal Article] Identification and characterization of endoplasmic reticulum-associated protein, ERp43 (2007)
  • Author(s): Nishikawa M, Kira Y, Yabunaka Y, Inoue M
  • Journal Title: Gene 386 Pages: 42-51
  • Peer Reviewed
• [Journal Article] The recovery of Mycobacterium avium-intracellulare complex (MAC) from the residential bathrooms of patients with pulmonary MAC (2007)
  • Author(s): Nishiuchi Y, Maekura R, Kitada S, Tamaru A, Taguri T, Kira Y, Hiraga T, Hirotani A, Yoshimura K, Miki M, Ito M
  • Journal Title: Clinical Infectious Diseases 45 Pages: 347-351
  • Peer Reviewed
• [Journal Article] In vitro effect of dehydroepiandrosterone sulfate on steroid receptors, aromatase, cyclooxygenase-2 expression, and steroid hormone production in preovulatory human granulose cells (2007)
  • Author(s): ElBeltagy K, Honda K, Ozaki K, Misugi T, Tokuyama O, Kimura M, Kira Y, Ishiko O
  • Journal Title: Fertility and sterility 88 Pages: 1135-1142
  • Peer Reviewed
• [Journal Article] The recovery of Mycobacterium avium-intracellulare complex (MAC) from the residential bathrooms of patients with pulmonary MAC (2007)
  • Author(s): Nishiuchi Y, Maekura R, Kitada S, Tamaru A, Taguri T, Kira Y, Hiraga T, Hirotani A, Yoshimura K, Miki M, Ito M.
  • Journal Title: Clinical Infectious Diseases 45 Pages: 347-351
  • Peer Reviewed
• [Journal Article] Identification and characterization of endoplasmic reticulum-associated protein,ERp43 (2007)
  • Author(s): Nishikavva M, Kira Y, Yabunaka Y, Inoue M.
  • Journal Title: Gene 386 Pages: 42-51
  • Peer Reviewed
• [Journal Article] In vitro effect of dehydroepiandrosterone sulfate on steroid receptors.aromatase,cyclooxygenase-2 expression,and steroid hormone production inpreovulator human sranulose cells (2007)
  • Author(s): ElBeltagy K, Honda K, Ozaki K, Misugi T, Tokuyama O, Kimur a M, Kira Y.Ishiko O
  • Journal Title: preovulatory human granulosa cells 88 Pages: 1135-1142
  • Peer Reviewed
• [Journal Article] Identification and characterization of endoplasmic reticulum-associated protein, ERp43. (2007)
  • Author(s): Nishikawa M, Kira Y, Yabunaka Y, Inoue M.
  • Journal Title: Gene 386・1-2 Pages: 42-51
• [Journal Article] A possible cooperation of SOD1 and cytochrome c in mitochondria-dependent apoptosis (2006)
  • Author(s): Li Q, Sato EF, Kira Y, Nishikawa M, Utsumi K, Inoue M
  • Journal Title: Free Radical Biology & Medicine 40 Pages: 173-181
  • Peer Reviewed
• [Journal Article] Curcuma Aromatica inhibits diabetic nephropathy in the rat (2006)
  • Author(s): Hong J Y, Sato EF, Kira Y, Nishikawa M, Shimada K, Inoue M
  • Journal Title: JOURNAL OF FOOD SCIENCE 71
  • Peer Reviewed
• [Journal Article] L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis (2006)
  • Author(s): Kira Y, Nishikawa M, Ochi A, Sato E, Inoue M
  • Journal Title: Brain Research 1070 Pages: 206-214
  • Peer Reviewed
• [Journal Article] L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis. (2006)
  • Author(s): Kira Y, Nishikawa M, Ochi A, Sato E, Inoue M.
  • Journal Title: Brain Research 1070・1 Pages: 206-214
• [Journal Article] A possible cooperation of SOD1 and cytochrome c in mitochondria-dependent apoptosis. (2006)
  • Author(s): Li Q, Sato EF, Kira Y, Nishikawa M, Utsumi K, Inoue M.
  • Journal Title: Free Radical Biology ＆ Medicine 40・1 Pages: 173-181
• [Journal Article] Curcuma Aromatica inhibits diabetic nephropathy in the rat (2006)
  • Author(s): Hong JY, Sato EE, Kira Y, Nishikawa M, Shimada K, Inoue M
  • Journal Title: JOURNAL OF FOOD SCIENCE 71・9
• [Presentation] The identification and Characterization of a GTPbinding protein with molecular weight of 45 kD : Gbp45 (2008)
  • Author(s): Yukimi Kira and Manabu Nishikawa
  • Organizer: Biochemistry and Molecular Biology 2008
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-09
• [Presentation] Identification and Characterization of a GTP-binding protein with molecular weight of 45 kD : Gbp45 (2008)
  • Author(s): Yukimi Kira, Manabu Nishikawa
  • Organizer: Biochemistry and Molecular Biology2008
  • Place of Presentation: KOBE
• [Presentation] Identification and Characterization of Endoplasmic Reticulum-Associated Protrm,ERp43 (2007)
  • Author(s): Kira Y, Nishikawa M, Inoue M
  • Organizer: Biochemistry and Molecular Biology 2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-12
• [Presentation] Analysis of methylation status in the promoter of interferon regulatory factor-2 in patients with late-onset psoriasis (2007)
  • Author(s): Hosomi N, Fukai1 K, Oiso N, Kira Y, Ohshimo T, Ishii M
  • Organizer: THE AMERICAN SOCIETY OF HUMAN GENETICS 57th ANNUAL MEETING
  • Place of Presentation: San Diego, California. USA
  • Year and Date: 2007-10-25
• [Presentation] Analysis of methylation status in the promoter of interferon regulatory factor-2 in Patients with late-onset psoriasis (2007)
  • Author(s): Hosomi N, Fukail K, Oiso N, Kira Y, Ohshimo T, Ishii M.
  • Organizer: THE AMERICAN SOCIETY OF HUMAN GENETICS57_th ANNUAL MEETING
  • Place of Presentation: San Diego,California
  • Year and Date: 2007-10-25
• [Presentation] 尋常性乾癬患者におけるInterferon regulatory factor 2 遺伝子プロモーター領域のメチル化解析 (2007)
  • Author(s): 細見尚子, 深井和吉, 大磯直毅, 吉良幸美, 石井正光
  • Organizer: 第3回加齢皮膚医学研究会
  • Place of Presentation: 大阪
  • Year and Date: 2007-06-16
• [Presentation] Identification and Characterization of Endoplasmic Reticulum-Associated Protein, ERp43 (2007)
  • Author(s): Kira Y , Nishikawa M, Inoue M
  • Organizer: Biochemistry and Molecular Biology 2007
  • Place of Presentation: YOKOHAMA
• [Presentation] L-Carnitine suppresses the onset of neuromuscular degeneration and increases the lifespan of mice with familial amyotrophic lateral sclerosis (2006)
  • Author(s): Yukimi Kira, Manabu Nishikawa, Yoriko Yabunaka, Eisuke Sato, Akemi Ochi, Masayasu Inoue
  • Organizer: 17th International SYMPOSIUM ON ALS/MND
  • Place of Presentation: YOKOHAMA
• [Presentation] L-Carnitine suppresses the onset of neuromuscular degeneration and increases the lifespan of mice with familial amyotrophic lateral sclerosis (2006)
  • Author(s): Yukimi Kira, Manabu Nishikawa, Yoriko Yabunaka, Eisuke Sato, Akemi Ochi, Masayasu Inoue
  • Organizer: 第20回国際分子生物・生化学会議(IUBMB)
  • Place of Presentation: 京都国際会館