Intracellular signal transduction in response to hypothermia

• Project/Area Number: 26670782
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Yamagata University
• Principal Investigator: Goto Kaoru 山形大学, 医学部, 教授 (30234975)
• Co-Investigator(Kenkyū-buntansha): 秋元 亮 山形大学, 医学部, 助教 (40594677)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: エネルギー代謝 / 脂質代謝酵素 / 低酸素 / エネルギーセンサー / ATP / 熱ショックタンパク質 / エネルギーストレス / ミトコンドリア / 呼吸 / ATP産生 / 低酸素ストレス / HIF / 細胞内情報伝達機構 / 培養細胞 / ジアシルグリセロールキナーゼ / 細胞内情報伝達系 / 塩化コバルト

Outline of Final Research Achievements

Upon tissue damage, hypothermia induces Hypoxia inducible factor (HIF), which suppresses energy expenditure and exerts a beneficial effect to damaged cells. In this study we examined the regulatory mechanism of the diacylglycerol kinase (DGK) family on HIF expression and energy metabolism. We found that after 24 h of 1% hypoxic conditions DGKzeta deficiency reduces HIF1alpha expression by 50%, activates energy sensor AMPK, and increases intracellular ATP levels. These results suggest that DGKzeta plays an important role in energy metabolism under hypoxic conditions.

Research Products

• [Journal Article] DGKζ ablation engenders upregulation of p53 level in the spleen upon whole-body (2018)
  • Author(s): Tanaka T, Iseki K, Tanaka K, Nakano T, Iino M, Goto K
  • Journal Title: Adv Biol Regul. Volume: 67 Pages: 93-100
  • DOI: 10.1016/j.jbior.2017.09.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reciprocal regulation of p53 and NF-κB by diacylglycerol kinaseζ. (2016)
  • Author(s): Tanaka T, Tsuchiya R, Hozumi Y, Nakano T, Okada M, Goto K.
  • Journal Title: Adv Biol Regul Volume: 60 Pages: 15-21
  • DOI: 10.1016/j.jbior.2015.09.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression and localization of the diacylglycerol kinase family and of phosphoinositide signaling molecules in the adrenal gland. (2015)
  • Author(s): Hozumi Y, Akimoto R, Suzuki A, Otani K, Watanabe M, Goto K.
  • Journal Title: Cell Tissue Res. Volume: 362 Issue: 2 Pages: 295-305
  • DOI: 10.1007/s00441-015-2199-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cellular expression and localization of DGKζ-interacting NAP1-like proteins in the brain and functional implications under hypoxic stress. (2014)
  • Author(s): Takahashi N, Hozumi Y, Tanaka T, Okada M, Iseki K, Hayasaka K, Goto K.
  • Journal Title: Histochem Cell Biol Volume: 142 Issue: 5 Pages: 461-471
  • DOI: 10.1007/s00418-014-1226-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] DGKζ under stress conditions: "To be nuclear or cytoplasmic, that is the question" (2014)
  • Author(s): Goto K, Tanaka T, Nakano T, Okada M, Hozumi Y, Topham MK, Martelli AM.
  • Journal Title: Advances in Biological Regulation Volume: 54 Pages: 242-253
  • DOI: 10.1016/j.jbior.2013.08.007
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] グルコース欠乏負荷条件下におけるζ型ジアシルグリセロールキナーゼの機能解析 (2018)
  • Author(s): 東海林 悠、田中 俊昭、欠畑 誠治、後藤 薫
  • Organizer: 第123回 日本解剖学会総会
• [Presentation] DGKzeta 結合蛋白NAP1L1 によるNF-kB転写調節を介したアポトーシス制御 (2017)
  • Author(s): 田中俊昭、後藤薫
  • Organizer: 第122回日本解剖学会総会
  • Place of Presentation: 長崎大学（長崎）
  • Year and Date: 2017-03-28
• [Presentation] , Regulation of p53 and NF-kB by DGKzeta (2016)
  • Author(s): Tanaka T, Goto K
  • Organizer: The American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] 生体ストレスを解剖する (2016)
  • Author(s): 後藤薫
  • Organizer: 第19回日本臨床救急医学会総会
  • Place of Presentation: ピッグパレットふくしま（郡山）
  • Year and Date: 2016-05-12
  • Invited
• [Presentation] ゼータ型DGKによるエネルギーセンサーAMPKの制御 (2016)
  • Author(s): 秋元 亮、田中 俊昭、八月朔日 泰和、川前 金幸、後藤 薫
  • Organizer: 第１２１回 日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
• [Presentation] Regulation of p53 and NF-kB by diacylglycerol kinase ζ. (2015)
  • Author(s): Goto K.
  • Organizer: Fifty-Six International Symposium on “Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues”
  • Place of Presentation: ボローニア、イタリア
  • Year and Date: 2015-10-05
  • Invited
• [Presentation] Cytoplasmic translocation of DGKzeta exerts a protective effect against p53-mediated cytotoxicity. (2014)
  • Author(s): Goto K, Tanaka T
  • Organizer: The American Society for Cell Biology Annual Meeting
  • Place of Presentation: Philadelphia Convention Center, Philadelphia, USA
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] 一酵素ファミリーから見た生命現象―脂質性二次メッセンジャー代謝酵素ジアシルグリセロールキナーゼの機能解析 (2014)
  • Author(s): 後藤薫
  • Organizer: 第60日本解剖学会
  • Place of Presentation: 福島県立医大、福島
  • Year and Date: 2014-09-06 – 2014-09-07
  • Invited