The role of novel metabolite, O-acetyl-ADP-Ribose

• Project/Area Number: 24689019
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: University of Toyama
• Principal Investigator: NAKAGAWA TAKASHI 富山大学, 先端ライフサイエンス拠点, 特命助教 (40610374)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: 代謝 / メタボローム / NAD

Outline of Final Research Achievements

In this study, I investigated the physiological role of novel metabolite, O-acetyl-ADP-Ribose (OAADPR). First, the system to measure the OAADPR was established by using LC/MS. Next, I focused on the enzyme, Nudt5, which catabolized the OAADPR. I generated the Nudt5- knocked down cell and examined the intracellular metabolism in these cells, and found that various NAD-related metabolites were altered in these cells.

Research Products

• [Int'l Joint Research] Washington University School of Medicine(米国)
• [Journal Article] Deletion of SIRT1 in myeloid cells impairs glucose metabolism with enhancing inflammatory response to adipose tissue hypoxia (2016)
  • Author(s): Akiko Takikawa, Isao Usui , Shiho Fujisaka, Masashi Ikutani, Satoko Senda, Shinpei Hattori, Koichi Tsuneyama, Yukiko Koshimizu, Ran Inoue, Ayumi Tanaka-Hayashi, Takashi Nakagawa, Yoshinori Nagai, Kiyoshi Takatsu, Toshiyasu Sasaoka, Hisashi Mori, Kazuyuki Tobe
  • Journal Title: Diabetology International Volume: 7 Issue: 1 Pages: 59-68
  • DOI: 10.1007/s13340-015-0213-3
  • NAID: 40020774323
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nmnat3 is not essential for the maintenance of mitochondrial NAD level in vivo. (2016)
  • Author(s): Yamamoto M, Hikosaka K, Mahmood A, Tobe K, Shojaku H, Nakagawa T
  • Journal Title: PLOS ONE Volume: 11(1) Issue: 1 Pages: e0147037-e0147037
  • DOI: 10.1371/journal.pone.0147037
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice. (2015)
  • Author(s): Yoon MJ, Yoshida M, Johnson S, Takikawa A, Usui I, Tobe K, Nakagawa T, Yoshino J, Imai SI.
  • Journal Title: Cell Metabolism Volume: 21(1) Issue: 5 Pages: 1-12
  • DOI: 10.1016/j.cmet.2015.04.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SnapShot: Sirtuins, NAD and Aging (2014)
  • Author(s): Nakagawa T, Guarente L
  • Journal Title: Cell Metabolism Volume: 20(1) Issue: 1 Pages: 192-192
  • DOI: 10.1016/j.cmet.2014.06.001
  • Peer Reviewed
• [Journal Article] Deficiency of Nicotinamide Mononucleotide Adenylyltransferase 3 (Nmnat3) Causes Hemolytic Anemia by Altering the Glycolytic Flow in Mature Erythrocytes. (2014)
  • Author(s): Hikosaka K, Ikutani M, Shito M, Kazuma K, Gulshan M, Nagai Y, Takatsu K, Konno H, Tobe K, Kanno H, Nakagawa T
  • Journal Title: J Biol Chem Volume: 289 (21) Pages: 14796-14811
  • Peer Reviewed
• [Journal Article] Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. (2014)
  • Author(s): Sasaki T, Kikuchi O, Shimpuku M, Susanti VY, Yokota-Hashimoto H, Taguchi R, Shibusawa N, Sato T, Tang L, Amano K, Kitazumi T, Kuroko M, Fujita Y, Maruyama J, Lee YS, Kobayashi M, Nakagawa T, Minokoshi Y, Harada A, Yamada M, Kitamura T.
  • Journal Title: Diabetologia Volume: 57 Issue: 4 Pages: 819-831
  • DOI: 10.1007/s00125-013-3140-5
  • Peer Reviewed / Open Access
• [Presentation] メタボロミクスを用いたNAD代謝の疾患生物学 (2015)
  • Author(s): 7.中川崇
  • Organizer: 第38回日本分子生物学会・第88回日本生化学会合同年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Elucidating physiological and pathological roles of NAD synthesis enzyme, Nmnat3. (2015)
  • Author(s): Nakagawa T
  • Organizer: International Society for Tryptophan Research Conference (ISTRY2015)
  • Place of Presentation: Grand Rapids, USA
  • Year and Date: 2015-09-16
  • Int'l Joint Research / Invited
• [Presentation] NAD Synthesis Enzyme, Nmnat3 Protects against High Fat Diet- and Age-Induced Obesity in Mice. (2015)
  • Author(s): Nakagawa T, Gulshan M
  • Organizer: FASEB Science Research conferences: NAD+ Metabolism and Signaling
  • Place of Presentation: Timmendorfer Strand, Germany.
  • Year and Date: 2015-08-09
  • Int'l Joint Research
• [Presentation] Deficiency of Nmnat3 in mice causes hemolytic anemia and increases the susceptibility to malaria infection. (2015)
  • Author(s): Nakagawa T, Mehmood A
  • Organizer: Gordon Conference: Red Cells.
  • Place of Presentation: Holderness, USA
  • Year and Date: 2015-06-28
  • Int'l Joint Research
• [Presentation] NAD Synthesis Enzyme, Nmnat3 Protects against High Fat Diet- and Age-Induced Obesity in Mice. (2015)
  • Author(s): Nakagawa T, Gulshan M
  • Organizer: Keystone symposia Conference: Obesity and the Metabolic Syndrome:Mitochondria and Energy Expenditure
  • Place of Presentation: Whistler, Canada
  • Year and Date: 2015-03-22 – 2015-03-27
• [Presentation] Role of NAD metabolism in disease. (2014)
  • Author(s): Nakagawa T
  • Organizer: The 5th International Symposium in Life Science in Toyama.
  • Place of Presentation: Toyama, Japan
  • Year and Date: 2014-12-11
• [Presentation] Physiological Function of NAD Synthesis Enzyme, Nmnat3 (2013)
  • Author(s): Nakagawa T, Hikosaka K
  • Organizer: Cold Spring Harbor Asia Meeting, Molecular Basis of Aging.
  • Place of Presentation: Suzhou, China