Toward the establishment of induced metabolic reprograming, a new strategy for organ protection

• Project/Area Number: 22659283
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Kyoto University
• Principal Investigator: HIROTA Kiichi 京都大学, 医学研究科, 准教授 (00283606)
• Co-Investigator(Kenkyū-buntansha): FUJIMORI Akira 独立行政法人放射線医学総合研究所, 重粒子医学センター, 研究員 (50314183)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: 低酸素 / 臓器保護 / 低酸素誘導性因子1 / プレコンディショニング / 分子生物学 / 低酸素誘導性因子

Research Abstract

We demonstrated that forced activation of hypoxiainducible factor 1(HIF-1) by the exogenous small molecule npropyl gallate(nPG) induced metabolic reprograming from cellular energy generation dependent on OXPHOS in mitochondria to glycolysisdominant one. Moreover, we indicated that nPG pretreatment induced HIF-1 activation and expression of glycolytic enzymes resulting in protection of brain against ischemia and reperfusion injury.

Research Products

• [Journal Article] Effects of n-propyl gallate on neuronal survival after forebrain ischemia in rats (2012)
  • Author(s): Y. Kawano, M. Kawaguchi, K. Hirota, S. Kai, N. Konishi, H. Furuya
  • Journal Title: Resuscitation Volume: 83 Issue: 2 Pages: 249-252
  • DOI: 10.1016/j.resuscitation.2011.07.024
  • Peer Reviewed
• [Journal Article] Hydrogen sulfide inhibits hypoxia- but not anoxia-induced hypoxia-inducible factor 1 activation in a von hippel-lindau- and mitochondria-dependent manner. (2011)
  • Author(s): 甲斐慎一、田中具治、大条紘樹、原田浩、岸本俊、鈴木堅悟、高淵聡史、竹永敬三、福田和彦、広田喜一
  • Journal Title: Antioxid Redox Signal Volume: 16 Issue: 3 Pages: 203-216
  • DOI: 10.1089/ars.2011.3882
  • Peer Reviewed
• [Journal Article] Fentanyl activates hypoxia-inducible factor 1 in neuronal SH-SY5Y cells and mice under non-hypoxic conditions in a μ-opioid receptor-dependent manner. (2011)
  • Author(s): 大条紘樹、甲斐慎一、田中具治、若松拓彦、岸本俊、鈴木堅悟、原田浩、高淵聡史、足立健彦、福田和彦、広田喜一
  • Journal Title: Eur J Pharmacol Volume: 667 Issue: 1-3 Pages: 144-152
  • DOI: 10.1016/j.ejphar.2011.06.014
  • Peer Reviewed
• [Journal Article] Detection of the onset of ischemia and carcinogenesis by hypoxiainducible transcription factor-based in vive bioluminescence imaging (2011)
  • Author(s): Harada, H., Inoue, M., Itasaka, S., Hirota, K., Morinibu, A., Shinomiya, K., Kadonosono, T., Kuchimaru, T., Yamada, S., Takahashi, Y., Murakami, A., Tani, T., Watanabe, H., Tanaka, T., Hirota, K., Inoue, M., et al
  • Journal Title: PLoS ONE Volume: 6 Pages: 2664-2664
  • Peer Reviewed
• [Journal Article] General anesthetics inhibit erythropoietin induction under hypoxic conditions in the mouse brain. (2011)
  • Author(s): 田中具治、甲斐慎一、小山智弘、大条紘樹、足立健彦、福田和彦、広田喜一
  • Journal Title: PLoS One Volume: 6 Issue: 12 Pages: 29378-29378
  • DOI: 10.1371/journal.pone.0029378
  • NAID: 120003726125
  • Peer Reviewed
• [Journal Article] 周術期医学としてのハイポキシア生物学の探究 (2011)
  • Author(s): 広田喜一
  • Journal Title: 麻酔 Volume: 60 Pages: 183-188
  • URL: http://jglobaljst.gojp/public/20090422/201102221994057673
• [Journal Article] 炎症の制御点としての低酸素誘導性因子 (2011)
  • Author(s): 広田喜一, 大条鉱樹, 甲斐慎一, 鈴木堅悟, 岸本俊, and松山智紀
  • Journal Title: 麻酔 Volume: 60 Pages: 69-74
  • URL: http://jglobaljst.gojp/public/20090422/201102269918990320
• [Journal Article] Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging (2011)
  • Author(s): Kadonosono T, Kuchimaru T, Yamada S, Takahashi Y. Murakami A, Watanabe H, Tani T, Inoue M, Tsukamoto T, Toyoda T, Tanaka T, Hirota K, Urano K, Machida K, Eto T, Ogura T, Tsutsumi H, Ito M, Hiraoka M, Kondoh G, Kizaka-Kondoh S
  • Journal Title: PLoS ONE Volume: 6(11) Issue: 11 Pages: e26640-e26640
  • DOI: 10.1371/journal.pone.0026640
  • Peer Reviewed
• [Journal Article] 炎症の制御点としての低酸素誘導性因子 (2011)
  • Author(s): 広田喜一, 他
  • Journal Title: 麻酔 Volume: 60
• [Journal Article] The intravenous anesthetic propofol inhibits lipopolysaccharideinduced hypoxiainducible factor 1 activation and suppresses the glucose metabolism in macrophages (2010)
  • Author(s): Tanaka, T., Takabuchi, S., Nishi, K., Oda, S., Wakamatsu, T., Daijo, H., Fukuda, K., and Hirota, K
  • Journal Title: J Anesth Volume: 24 Pages: 54-60
  • Peer Reviewed
• [Journal Article] Persisting mild hypothermia suppresses hypoxia-inducible factor-1alpha protein synthesis and hypoxia-inducible factor-1-mediated gene expression. (2010)
  • Author(s): 田中具治、若松拓彦、大条紘樹、小田聖子、甲斐慎一、足立健彦、木坂(近藤)科江、福田和彦、広田喜一
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 298 Issue: 3 Pages: 661-671
  • DOI: 10.1152/ajpregu.00732.2009
  • Peer Reviewed
• [Journal Article] Persisting mild hypothermia suppresses hypoxia-inducible factor 1{alpha} protein synthesis and HIF-1-mediated gene expression. (2010)
  • Author(s): Tanaka, Tomohiro, 他
  • Journal Title: Am J Physiol Regul Integr Comp Physiol. Volume: 293
  • Peer Reviewed
• [Journal Article] The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages. (2010)
  • Author(s): Tanaka, Tomohiro, 他
  • Journal Title: Journal of Anesthesia Volume: 24 Pages: 54-60
  • Peer Reviewed
• [Journal Article] Involvement of decreased hypoxiainducible factor 1 activity and resultant GI-S cell cycle transition in radioresistance of perinecrotic tumor cells
  • Author(s): Zuo, Y., Zhao, T., Itasaka, S., Zeng, L., Yoem, C., Hirota, K., Suzuki, K., Morinibu, A., Shinomiya, K., on, G., et al.
  • Journal Title: Oncogene Volume: (In Press)
  • Peer Reviewed
• [Journal Article] グルタミノリシス
  • Author(s): 広田喜一
  • Journal Title: Inがんと代謝 Volume: (In Press)
• [Journal Article] Cancer cells that survive radiation therapy acquire HIF-l activity and translocate towards tumour blood vessels
  • Author(s): Harada, H., Inoue, M., Itasaka, S., Hirota, K., Morinibu, A., Shinomiya, K., Kadonosono, T., Kuchimaru, T., Yamada, S., Takahashi, Y., Murakami, A., Tani, T., Watanabe, H., Tanaka, T., Hirota, K., Inoue, M., et al
  • Journal Title: Nat Commun Volume: 3 Pages: 783-783
  • Peer Reviewed
• [Presentation] 炎症の制御点としての低酸素誘導性因子 (2012)
  • Author(s): 広田喜一, 他
  • Organizer: 日本麻酔科学会第58回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-05-20
• [Presentation] 周術期医学としてのハイポキシア生物学の探究 (2012)
  • Author(s): 広田喜一
  • Organizer: 日本麻酔科学会第58回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-05-19
• [Presentation] 静脈麻酔薬が膵b細胞のインスリン分泌に与える影響の検討 (2011)
  • Author(s): 鈴木堅悟, 広田喜一, 大条紘樹, 甲斐慎一, 松山智紀, 福田
  • Organizer: 第18回日本静脈麻酔学会
  • Year and Date: 2011-11-16
• [Presentation] Isoflurane selectively inhibits the activation of hypoxia-inducible factor 2 and the induction of erythropoietin under hypoxic conditions in mouse brain (2011)
  • Author(s): Kiichi Hirota, Tomoharu Tanaka, Shinichi Kai, Tomohiro Koyama, Hiroki Daijo, Kengo Suzuki, Takehiko Adachi, Kazuhiko Fukuda
  • Organizer: 2011 Annual Meeting, American Society of Anesthesiologists
  • Place of Presentation: Chicago
  • Year and Date: 2011-10-16
• [Presentation] Differential role of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E1 in vascular-derived cells under non-hypoxic conditions (2011)
  • Author(s): Kengo Suzuki, Satoshi Takabuchi, Hiroki Daijo, Shinichi Kai, Tomonori Matsuyama, Shin Kurosawa, Kazuhiko Fukuda, Kiichi Hirota
  • Organizer: 2011 Annual Meeting, American Society of Anesthesiologists
  • Place of Presentation: Chicago
  • Year and Date: 2011-10-16
• [Presentation] Hydrogen sulfide inhibits hypoxia-induced HIF-1 activation in a mitochondria-dependent manner (2011)
  • Author(s): Shinichi Kai, Tomoharu Tanaka, Hiroki Daijo, Shun Kishimoto, Kengo Suzuki, Satoshi Takabuchi, Takuhiko Wakamatsu, Kazuhiko Fukuda, Kiichi Hirota
  • Organizer: 2011 Annual Meeting, American Society of Anesthesiologists
  • Place of Presentation: Chicago
  • Year and Date: 2011-10-16
• [Presentation] Fentanyl activates hypoxia-inducible factor 1 in neuronal SH-SY5Y cells and mice under non-hypoxic conditions in aμ-opioid receptor-dependent manner (2011)
  • Author(s): H. Daijo, K. Hirota, S. Kai1, T. Matsuyama, K. Suzuki T. Tanaka, T. Wakamatsu, K. Fukuda
  • Organizer: 2011 Annual Meeting, American Society of Anesthesiologists
  • Place of Presentation: Chicago
  • Year and Date: 2011-10-15
• [Presentation] イソフルランは低酸素によるエリスロポエチンの上昇を抑制する (2011)
  • Author(s): 甲斐慎一, 田中具治、鈴木堅悟, 大条鉱樹、広田喜一、福田和彦
  • Organizer: 日本麻酔科学会第58回学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-05-20
• [Presentation] プロスタグランディンElはHIF-l1活性化、VEGF発現を介して血管透過性を充進させる (2011)
  • Author(s): 鈴木堅悟、広田喜一、大条鉱樹、甲斐慎一、岸本俊、福田和彦
  • Organizer: 日本麻酔科学会第58回学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-05-20
• [Presentation] 炎症の制御点としての低酸素誘導性因子 (2011)
  • Author(s): 広田喜一、大条鉱樹、甲斐慎一、鈴木堅悟, 岸本俊、松山智紀
  • Organizer: 日本麻酔科学会第58回学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-05-20
• [Presentation] タバコ煙抽出物はヒト肺胞H型上皮細胞株(As4g)において低酸素誘導性因子1(hypoxia-inducible factor 1HIF-l1)を活性化する (2011)
  • Author(s): 大条紘樹、鈴木堅固, 岸本俊、甲斐慎一、広田喜一、福田和彦
  • Organizer: 日本麻酔科学会第58回学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-05-19
• [Presentation] 周術期医学としてのハイポキシア生物学の探求 (2011)
  • Author(s): 広田喜一
  • Organizer: 日本麻酔科学会第58回学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-05-19
• [Presentation] タバコ煙抽出物は低酸素誘導性因子1(hypoxia-inducible factor 1 : HIF-1)を活性化する (2011)
  • Author(s): 大条鉱樹, 他
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 北海道大学学術交流会館,札幌市
  • Year and Date: 2011-01-30
• [Presentation] 硫化水素が低酸素誘導性HIF-1活性化に及ぼす影響 (2011)
  • Author(s): 甲斐慎一, 他
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 北海道大学学術交流会館, 札幌市
  • Year and Date: 2011-01-30
• [Presentation] 硫化水素が低酸素誘導性遺伝子応答に及ぼす影響The effects of hydrogen sulfide on thecellular hypoxia-induced gene responses meditated by HIF-1 (2010)
  • Author(s): 甲斐惧一、大条紘樹、田中具治、広田喜一、福田和彦
  • Organizer: 日本麻酔科学会第57回学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-06-04
• [Presentation] 全身麻酔下では、低酸素による脳内エリスロポエチン発現誘導が抑制される (2010)
  • Author(s): 田中具治、、大条紘樹、甲斐慎一、小山智弘、福田和彦
  • Organizer: 日本麻酔科学会第57回学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-06-04
• [Presentation] フェンタニルはオピオイド受容体を介し、低酸素誘導性因子(hypoxia-induciblefactor 1 : HIF-1)を活性化するFentanyl induces hypoxiainducible factor 1 activation via opioid receptormediated signaling pathways (2010)
  • Author(s): 大条紘樹、広田喜一、甲斐慎一、田中具治、福田和彦
  • Organizer: 日本麻酔科学会第57回学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-06-03
• [Presentation] 硫化水素が低酸素誘導性HIF-1活性化に及ぼす影響 (2010)
  • Author(s): 甲斐慎一, 鈴木堅悟, 広田喜一, 大条紘樹, 岸本俊
  • Organizer: 第6回がんとハイポキシア研究会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-01-30
• [Presentation] タバコ煙抽出物は低酸素誘導性因子1(hypoxia-induciblefactor1 : HIF-1)を活性化する (2010)
  • Author(s): 大条紘樹, 広田喜一, 鈴木堅悟, 甲斐慎一, 岸本俊
  • Organizer: 第6回がんとハイポキシア研究会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-01-30
• [Book] Hypoxia andhypoxia-inducible factor in inflammation. InCHRONIC INFLAMMATION : NUTRITIONAL & THERAPEUTIC INTERVENTIONS, S. Roy
  • Author(s): Hirota, K.
  • Publisher: Taylor & Francis