The Metabolome Analysis: Association with pathogenesis of COPD in Leukocyte

• Project/Area Number: 20790575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Keio University
• Principal Investigator: TAKAMIYA Rina Keio University, 医学系研究科, 特任研究員(常勤) (70365419)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: COPD / 白血球 / 赤血球 / メタボローム解析 / 活性酸素 / ペントースリン酸回路 / 代謝 / 酸化ストレス / coPD / タバコ / 代謝解析

Research Abstract

申請者は、キャピラリー電気泳動-質量分析装置を用いたメタボローム解析より、タバコ煙抽出液は、細胞内糖代謝流速を解糖系からペントースリン酸回路にシフトさせ、ヌクレオチド生成も亢進させ、細胞内糖代謝応答に異常を引き起こす事で、白血球の機能や生存を制御している可能性が示唆する可能性を示した。そのため、この回路の異常が白血球の機能異常を齎し、慢性閉塞性肺疾患(COPD)の病態修飾に寄与すると考えられた。

Research Products

• [Journal Article] Levy The Anti-Inflammatory and Proresolving Mediator Resolvin E1 Protects Mice from Bacterial Pneumonia and Acute Lung Injury (2010)
  • Author(s): Hiroyuki Seki, Koichi Fukunaga, Arita, Makoto H, iroyuki Arai, Hiroki Nakanish, Ryo Taguchi, Toru Miyasho, Rina Takamiya, Koichiro Asano, Akitochi Ishizaka, Jyunzo Takeda, Bruce D
  • Journal Title: The Journal of Immunology 184 Pages: 836-843
  • Peer Reviewed
• [Journal Article] The anti-inflammatory and pro-resolving mediator Resolvin E1 protects mice from bacterial pneumonia and acute lung injury (2010)
  • Author(s): Seki H, Fukunaga K, Arita M, Arai H, Nakanishi H, Taguchi R, Miyasho T, Takamiya R, Asano K, Ishizaka A, Takeda J, Levy BD
  • Journal Title: Journal of Immunology 184(2) Pages: 836-843
  • Peer Reviewed
• [Journal Article] Rescue of anaemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes (2009)
  • Author(s): Yoshito Iuchi, Futoshi Okada, Rina Takamiya, Noriko Kibe, Satoshi Tsunoda, Osamu Nakajima, Kazuyo Toyoda, Ritsuko Nagae, Makoto Suematsu, Tomoyoshi Soga, Koji Uchida, Jyunichi Fujii
  • Journal Title: Biochemical Journal 422 Pages: 313-320
  • Peer Reviewed
• [Journal Article] Perrella High-mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1-deficient mice (2009)
  • Author(s): Rina Takamiya, Chi-Chih Hung, Sean R. Hall, Koichi Fukunaga, Takashi Nagaishi, Toshitaka Maeno, Caroline Owen, Alvaro A. Macias, Laura E. Fredenburgh, Akitoshi Ishizaka, Richard S. Blumberg, Rebecca M. Baron, Mark A.
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology 41 Pages: 129-135
  • Peer Reviewed
• [Journal Article] Rescue of Anemia and Autoimmune Responses in Cu, Zn-Superoxide Dismutase Gene (SOD1)-Deficient Mice by Transgenic Expression of Human SOD1 in Erythrocytes (2009)
  • Author(s): Iuchi Y, Okada F, Takamiya R, Kibe N, Tsunoda S, Nakajima S, Toyoda K, Nagae R, Suematsu M, Soga T, Uchida K, Fujii J
  • Journal Title: Biochemical Journal 422 Pages: 313-320
  • Peer Reviewed
• [Journal Article] High mobility group box 1 protein in the absence of HO-1 : Role during endotoxemia in mice (2009)
  • Author(s): Takamiya R, Hung CC, Hall SR, Fukunaga K, Nagaishi T, Maeno T, Macias AA, Owen CA, Fredenburgh LE, Ishizaka A, Blumberg RS, Baron RM, Perrella MA
  • Journal Title: American Journal of Respiratory Cell and Morecular Biology 41 Pages: 129-135
  • Peer Reviewed
• [Journal Article] High Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1 Deficient Mice (2009)
  • Author(s): Rina Takamiya
  • Journal Title: Am J Respir Cell Mol Biol (In press)
  • Peer Reviewed
• [Journal Article] High mobility group A1 protein mediates human nitric oxide synthase 2 gene expression (2008)
  • Author(s): Rina Takamiya, Rebecca M. Baron, Shaw-Fang Yet, Matthew D. Layne, Mark A. Perrella
  • Journal Title: FEBS Letters 582 Pages: 810-814
  • Peer Reviewed
• [Journal Article] High mobility group Al protein mediates human nitric oxide synthase 2 geneexpression (2008)
  • Author(s): Rina Takamiya
  • Journal Title: FEBS Lett 582 Pages: 810-814
  • Peer Reviewed
• [Presentation] Cigarette smoke extract induces bisecting-GlcNAc modification in RAW264. 7 murine macrophage (2009)
  • Author(s): Rina Takamiya
  • Organizer: Japanese-Giessen GlycoWorkshop
  • Place of Presentation: ギーセン、ドイツ
  • Year and Date: 2009-11-07
• [Presentation] Cigarette smoke extract induces bisecting-G1cNAc modification in RAW26 4.7 murine macrophage (2009)
  • Author(s): Takamiya R, Ohtsubo K, Takamatsu S, Taniguchi N, Angata T
  • Organizer: Japanese-Giessen-GlycoWorkshop
  • Place of Presentation: Justus-Liebig-University, Giessen, Germany
  • Year and Date: 2009-11-07
• [Presentation] タバコ煙によるマクロファージ機能低下におけるレゾルビンE1の有用性 (2009)
  • Author(s): 高宮里奈
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] タバコ煙によるマクロファージ機能低下におけるレゾルビンE1の有用性の検討 (2009)
  • Author(s): 高宮里奈、福永興壱、有田誠、宮田純、末松誠、浅野浩一郎、石坂彰敏
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際展示場、神戸
  • Year and Date: 2009-10-22
• [Presentation] Cigarette smoke extract induces bisecting-GlcNAc modification in RAW264. 7 murine macrophage (2009)
  • Author(s): Rina Takamiya
  • Organizer: 20th Joint Glycobiology Meeting
  • Place of Presentation: ケルン、ドイツ
• [Presentation] Cigarette smoke extract induces bisecting-G1cNAc modification in RAW26 4.7 murine macrophage (2009)
  • Author(s): Takamiya R, Ohtsubo K, Takamatsu S, Taniguchi N, Angata T
  • Organizer: 20th Joint Glycobiology Meeting
  • Place of Presentation: Maternushaus, Cologne, Germany
• [Presentation] 網羅的代謝解析を中心としたアクロレインに曝露された赤血球の機能解明 (2008)
  • Author(s): 高宮里奈
  • Organizer: 第31回日本生化学会・分子生物学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Circulating levels of HMGB1 are exaggerated in HO-1 null mice during endotoxemia (2008)
  • Author(s): Rina Takamiya
  • Organizer: American Thoracic Society International Meeting 2008
  • Place of Presentation: トロント、カナダ
  • Year and Date: 2008-05-19
• [Presentation] Circulating levels of HMGB1 are exaggerated in HO-1 null mice during endotoxemia (2008)
  • Author(s): Rina Takamiya
  • Organizer: American Thoracic Society International Meeting 2008
  • Place of Presentation: カナダ トロント
  • Year and Date: 2008-05-19