Functional Analysis of Muscle Specific NAD/NADH Dehydrogenase, and Establishment as a Biomarker for Cardiac Dysfunction.

• Project/Area Number: 25670392
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyushu University
• Principal Investigator: SUNAGAWA Kenji 九州大学, 医学(系)研究科(研究院), 教授 (50163043)
• Co-Investigator(Kenkyū-buntansha): ARAI Shinobu 九州大学, 病院学術研究員 (30529970) ; 井手 友美 九州大学, 医学(系)研究科(研究院), 講師 (90380625)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: カルシウム / 筋肥大 / 心肥大 / 心不全 / DHRS7C / デヒドロゲナーゼ / 筋小胞体

Outline of Final Research Achievements

DHRS7C (Dehydrogenase/Reductase (SDR Family) Member 7C) is a novel unknown molecule expressed specifically in heart and skeletal muscle. We found DHRS7c correlates strongly with left ventricular (LV) function from . We herein aimed to investigate the role of DHRS7C in the development of heart failure and to establish as a diagnostic marker of LV dysfunction. We found that DHRS7C is a major regulator of cellular calcium homeostasis, locating in sarcoplasmic reticulum. Moreover, we also found the expression of DHRS7C is regulated by hypoxia inducible factor (HIF-1). We established a suitable condition of antibodies and protocol for ELISA. We found further determination of serum pretreatment condition is necessary in order to obtain higher sensitivity and to reduce background. We are working for measuring the level of DHRS7C in serum from healthy volunteer and heart failure patients.

Research Products

• [Journal Article] Overexpression of TFAM or Twinkle Increases mtDNA Copy Number and Facilitates Cardioprotection Associated with Limited Mitochondrial Oxidative Stress. (2015)
  • Author(s): Ikeda M, Ide T, Fujino T, Arai S, Saku K, Kakino T, Tyynismaa H, Yamasaki T,Yamada K, Kang D, Suomalainen A, Sunagawa K.
  • Journal Title: PLoS One. Volume: 10 Issue: 3 Pages: e0119687-e0119687
  • DOI: 10.1371/journal.pone.0119687
  • Peer Reviewed / Open Access
• [Presentation] DHRS7C NAD/NADH dehydrogenase catalytic core domain is essential for cellular calcium homeostasis and cell morphology. (2014)
  • Author(s): Arai, S., Ide. T., Ikeda, M., Hirano, K., Matsuo, Y., Sunagawa, S.
  • Organizer: 第31回国際心臓研究学会 (ISHR)
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-28 – 2014-11-29
• [Presentation] ベッドサイドとラボで学んだ心筋症 (2013)
  • Author(s): 井手友美
  • Organizer: 東京心臓病理フォーラム
  • Place of Presentation: 東京
  • Invited