Investigation on the molecular mechanism of maintenance of oxygen homeostasis by hypoxia-inducible factor 1 system

• Project/Area Number: 18390429
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Kyoto University
• Principal Investigator: HIROTA Kiichi Kyoto University, 大学院・医学研究科, 講師 (00283606)
• Co-Investigator(Kenkyū-buntansha): TAKABUCHI Satoshi 京都大学, 大学院・医学研究科, 研究員 (90402841) ; KONDOH Shinae 京都大学, 大学院・医学研究科, 特任教授 (40314182) ; HARADA Hiroshi 京都大学, 大学院・医学研究科, 特任講師 (80362531)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,910,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥2,010,000); Fiscal Year 2008: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2006: ¥7,200,000 (Direct Cost: ¥7,200,000)
• Keywords: 周術期管理学 / 遺伝子 / 細胞 / 低酸素 / シグナル伝達 / 転写因子 / HIF-1 / ストレス / 細胞・組織 / 発現制御

Research Abstract

酸素濃度感知性転写因子であるhypoxia-inducible factor 1(HIF-1 ; 低酸素誘導性因子1)と低酸素センサーの活性を指標に酸素ホメオスターシスを分子生物学を援用しリアルタイムでモニターする実験系を構築し、大きく分類して以下の実験結果を得た。
培養細胞、実験動物を用いてHIF-1活性化をアッセイする実験系を確立した。In vitro実験系で細胞酸素消費測定系を確立した。マウスを用いてHIF-1 の活性化をリアルタイムで検出する実験系を確立した。

Research Products

• [Journal Article] The calcium channel blocker cilnidipine selectively suppresses hypoxia-inducible factor 1 activity in vascular cells (2009)
  • Author(s): Oda S, Oda T, Takabuchi S, Nishi K, Wakamatsu T, Tanaka T, Adachi T, Fukuda K, Nohara R, Hirota K
  • Journal Title: Eur J Pharmacol 606 Pages: 130-6
  • Peer Reviewed
• [Journal Article] The calcium channel blocker cilnidipine selectively suppresses hypoxiainducible factor 1 activity in vascular cells (2009)
  • Author(s): Oda, Seiko
  • Journal Title: Eur J Pharmacol. 606 Pages: 130-136
  • Peer Reviewed
• [Journal Article] 低酸素応答と低酸素センサー (2008)
  • Author(s): 広田喜一, 田中具治
  • Journal Title: Life Support and Anesthesia 15 Pages: 238-43
• [Journal Article] ハイポキシア生物学-酸素代謝からみる生命現象の方程式 (2008)
  • Author(s): 広田喜一
  • Journal Title: 医学のあゆみ 225
• [Journal Article] Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner (2008)
  • Author(s): Oda S, Oda T, Nishi K, Takabuchi S, Wakamatsu T, Tanaka T, Adachi T, Fukuda K, Semenza GL, Hirota K
  • Journal Title: PLoS ONE 3 Pages: 2215-2215
  • Peer Reviewed
• [Journal Article] LPS induces hypoxia-inducible factor 1 activation in macrophage-differentiated cells in a reactive oxygen species-dependent manner (2008)
  • Author(s): Nishi K, Oda T, Takabuchi S, Oda S, Fukuda K, Adachi T, Semenza GL, Shingu K, Hirota K
  • Journal Title: Antioxid Redox Signal 10 Pages: 983-96
  • Peer Reviewed
• [Journal Article] n-Propyl gallate activates hypoxia-inducible factor 1 by modulating intracellular oxygen-sensing systems (2008)
  • Author(s): Kimura M, Takabuchi S, Tanaka T, Murata M, Nishi K, Oda S, Oda T, Kanai M, Fukuda K, Kizaka-Kondoh S, Adachi T, Takabayashi A, Semenza GL, Hirota K
  • Journal Title: Biochem J 411 Pages: 97-105
  • Peer Reviewed
• [Journal Article] Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner (2008)
  • Author(s): Oda, Seiko
  • Journal Title: PLoS ONE 3
  • Peer Reviewed
• [Journal Article] LPS induces hypoxia-inducible factor 1 activation in macrophage differentiated cells in a reactive oxygen species-dependent manner (2008)
  • Author(s): Nishi, Kenichiro
  • Journal Title: Antioxid Redox Signal 10 Pages: 983-996
  • Peer Reviewed
• [Journal Article] LPS induces hypoxia-inducible factor 1 activation in macrophage-differentiated cells in a reactive oxygen species-dependent manner (2008)
  • Author(s): Nishi, K., et. al.
  • Journal Title: Antioxid Redox Signal. 10 Pages: 983-996
  • Peer Reviewed
• [Journal Article] n-Propyl gallate activates hypoxia-inducible factor 1by modulating intracellular oxygen-sensing systems (2008)
  • Author(s): Kimura, M., et. al.
  • Journal Title: Biochemical Journal 411 Pages: 97-105
  • Peer Reviewed
• [Journal Article] 細胞の低酸素応答機構-低酸素センサーを巡る論争 (2007)
  • Author(s): 広田喜一
  • Journal Title: 実験医学 25 Pages: 2120-6
• [Journal Article] Inhibitory Effect of 6-Formylpterin on HIF-1alpha Protein Accumulation (2007)
  • Author(s): Sommani P, Yamashita K, Miyoshi T, Tsunemine H, Kodaki T, Mori H, Hirota K, Arai T, Sasada M, Makino K
  • Journal Title: Biol Pharm Bull 30 Pages: 2181-4
  • Peer Reviewed
• [Journal Article] Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-g in human proximal renal tubular cells (2007)
  • Author(s): Li X, Kimura H, Hirota K, Sugimoto H, Kimura N, Takahashi N, Fujii H, Yoshida H
  • Journal Title: Nephrol Dial Transplant 22 Pages: 1041-51
  • Peer Reviewed
• [Journal Article] Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer (2007)
  • Author(s): Hiraga T, Kizaka-Kondoh S, Hirota K, Hiraoka M, Yoneda T
  • Journal Title: Cancer research 67 Pages: 4157-63
  • Peer Reviewed
• [Journal Article] Exhaled carbon monoxide levels change in relation to inspired oxygen fraction during general anesthesia (2007)
  • Author(s): Adachi T, Hirota K, Hara T, Sasaki Y, Hara Y
  • Journal Title: Anesth Analg 105 Pages: 696-9
  • Peer Reviewed
• [Journal Article] 細胞の低酸素応答機構-低酸素センサーを巡る論争 (2007)
  • Author(s): 広田 喜一
  • Journal Title: 実験医学 25 Pages: 2120-2126
• [Journal Article] Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-g in human proximal renal tubular cells (2007)
  • Author(s): Li, X. 他8名
  • Journal Title: Nephrol. Dial. Transplant 22 Pages: 1041-1051
• [Journal Article] 低酸素センサー-細胞は低酸素をいかに関知するか- (2006)
  • Author(s): 広田喜一
  • Journal Title: Anesthesia Network 10 Pages: 11-5
• [Journal Article] Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase (2006)
  • Author(s): Tsukiyama F, Nakai Y, Yoshida M, Tokuhara T, Hirota K, Sakai A, Hayashi H, Katsumata T
  • Journal Title: Biochem Biophys Res Commun 35 Pages: 234-9
  • Peer Reviewed
• [Journal Article] Activation of hypoxia-inducible factor 1 during macrophage differentiation (2006)
  • Author(s): Oda T, Hirota K, Nishi K, Takabuchi S, Oda S, Yamada H, Arai T, Fukuda K, Kita T, Adachi T, Semenza GL, Nohara R
  • Journal Title: Am J Physiol Cell Physiol 291 Pages: 104-13
  • Peer Reviewed
• [Journal Article] Regulation of angiogenesis by hypoxia-inducible factor 1 (2006)
  • Author(s): Hirota K, Semenza GL
  • Journal Title: Crit Rev Oncol Hematol 59 Pages: 15-26
  • Peer Reviewed
• [Journal Article] Activation of hypoxia-inducible factor 1 during macrophage differentiation (2006)
  • Author(s): Oda, T. 他12名
  • Journal Title: Am J Physiol Cell Physiol 291
• [Journal Article] Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase (2006)
  • Author(s): Tsukiyama, F. 8名
  • Journal Title: Biochem Biophys Res Commun 351 Pages: 234-239
• [Journal Article] Regulation of angiogenesis by hypoxia-inducible factor 1 (2006)
  • Author(s): Hirota, K., Semenza, GL.
  • Journal Title: Crit Rev Oncol Hematol 59 Pages: 15-26
• [Presentation] 低酸素性遺伝子応答に温度変化が及ぼす影響 (2008)
  • Author(s): 田中具治, 他
  • Organizer: 日本麻酔科学会第54回学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-06-12
• [Presentation] 低酸素性遺伝子応答に温度変化が及ぼす影響 (2008)
  • Author(s): 田中具治
  • Organizer: 日本麻酔科学会第55回学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-06-12
• [Presentation] Macrophage migration inhibitory factor activates hypoxia-inducible factor 1 under hypoxic conditions in a p53-depenent manner (2008)
  • Author(s): Kiichi Hirota, Seiko Oda, Satoshi Takabuchi, Takuhiko Wakamatsu, Tomoharu Tanaka, Kazuhiko Fukuda
  • Organizer: Keystone symposia Molecular, cellular, physiologica, and phathogenic responses to hypoxia
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2008-01-16
• [Presentation] The calcium channel blocker cilnidipine selectively suppresses hypoxia-inducible factor 1 activity in vascular endothelial and smooth muscle cells (2008)
  • Author(s): Takehiko Adachi, Seiko Oda, Satoshi Takabuchi, Kenichiro Nishi, Kiichi Hirota
  • Organizer: 2008Annual Meeting, American Society of Anesthesiologists
  • Place of Presentation: Orland
• [Presentation] Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner (2007)
  • Author(s): 広出 喜一, 他
  • Organizer: 第5回がんとハイポキシア研究会
  • Place of Presentation: 千葉県 柏市
  • Year and Date: 2007-12-01
• [Presentation] 低酸素誘導性遺伝子応答に低温が及ぼす影響 (2007)
  • Author(s): 田中具治, 他
  • Organizer: 日本麻酔科学会第54回学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2007-06-01
• [Presentation] リドカインは上皮成長因子受容体シグナル伝達系非依存的に細胞増殖を抑制する (2007)
  • Author(s): 若松拓彦, 他
  • Organizer: 日本麻酔科学会第54回学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2007-05-31
• [Presentation] 生体の低酸素応答の分子生物学 : 基礎から臨床応用まで (2006)
  • Author(s): 広田喜一
  • Organizer: 日本麻酔科学会第53回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2006-06-01
• [Presentation] 低酸素誘導性遺伝子発現に及ぼすチオペンタールの影響 (2006)
  • Author(s): 若松拓彦, 他
  • Organizer: 日本麻酔科学会第53回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2006-06-01
• [Book] 周術期の呼吸管理(低酸素性肺障害の分子生物学) (2007)
  • Author(s): 広田喜一
  • Publisher: 克誠堂出版