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

2011 Fiscal Year Final Research Report

• 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
• 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

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] Hydrogen sulfide inhibits hypoxia but not anoxiainduced hypoxiainducible factor 1 activation in a von hippellindau andmitochondriadependent manner (2012)
  • Author(s): Kai, S., Tanaka, T., Daijo, H., Harada, H., Kishimoto, S., Suzuki, K., Takabuchi, S., Takenaga, K., Fukuda, K., and Hirota, K
  • Journal Title: Antioxidants & redox signaling Volume: 16 Pages: 203-216
  • DOI: Doi:10.1089/ars.2011.3882
  • Peer Reviewed
• [Journal Article] Effects of npropyl gal late on neuronal survival after forebrain ischemia in rats (2012)
  • Author(s): Kawano, Y., Kawaguchi, M., Hirota, K., Kai, S., Konishi, N., and Furuya, H
  • Journal Title: Resuscitation Volume: 83 Pages: 249-252
  • DOI: Doi:10.1016/j.resuscitation.2011.07.024
  • Peer Reviewed
• [Journal Article] Fentanyl activates hypoxiainducible factor 1 in neuronal SH-SYsY cells and mice under nonhypoxic conditions in a muopioid receptordependent manner (2011)
  • Author(s): Daijo, H., Kai, S., Tanaka, T., Wakamatsu, T., Kishimoto, S., Suzuki, K., Harada, H., Takabuchi, S., Adachi, T., Fukuda, K., Hirota, K
  • Journal Title: European journal of pharmacology Volume: 667 Pages: 144-152
  • DOI: 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
  • DOI: Doi:10.1038/ncommsli86
  • Peer Reviewed
• [Journal Article] General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain (2011)
  • Author(s): Tanaka, T., Kai, S., Koyama, T., Daijo, H., Adachi, T., Fukuda, K., and Hirota, K
  • Journal Title: PLoS ONE Volume: 6 Pages: 29378
  • DOI: Doi:10.1371/journal.pone.0029378
  • 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] 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
  • DOI: Doi:10.1007/soo540-009-0829-1
  • Peer Reviewed
• [Journal Article] Persisting mild hypothermia suppresses hypoxiainducible factorlalpha protein synthesis and hypoxiainducible factorlmediated gene expression. American journal of physiology Regulatory (2010)
  • Author(s): Tanaka, T., Wakamatsu, T., Daijo, H., Oda, S., Kai, S., Adachi, T., KizakaKondoh, S., Fukuda, K., and Hirota, K.
  • Journal Title: integrative and comparative physiology Volume: 298 Pages: 661-671
  • DOI: Doi:10.1152/ajpregu.00732.2009
  • 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
  • DOI: Doi:10.1038/ncommsli86
  • Peer Reviewed
• [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] 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