Functional analysis of novel phosphoinositide metabolites

• Project/Area Number: 15K18857
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Akita University
• Principal Investigator: Nakanishi Hiroki 秋田大学, 生体情報研究センター, 助教 (10466740)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 質量分析 / リピドミクス / ホスホイノシタイド / 生理活性 / イノシトールリン脂質 / 新規リン脂質 / 質量分析法 / 同定

Outline of Final Research Achievements

Phosphoinositide (PIP) is a membrane phospholipid composed of diacylglycerol and a D-myo-inositol head group. In mammals, the hydroxyl groups at the D3, D4 and D5 positions of the inositol ring can be phosphorylated to yield seven phosphoinositide derivatives. Recently, we developed high sensitivity PIPs detection method using LC-MS/MS system. Additionally, in the process of detecting PIPs in various biological samples, we found lysoPIPs which is detected at high levels in mouse cancer tissue. The aim of this study is to elucidate the physiological functions of PIPs and novel lysoPIPs and the pathological mechanism caused by PIPs metabolic abnormality. Future work, we aim to establish non-invasive biomarkers using blood sample. The development of novel biomarkers using phosphoinositide profiling is a world's first and an epoch-making attempt.

Research Products

• [Journal Article] Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia. (2017)
  • Author(s): Matsumoto J, Nakanishi H, Kunii Y, Sugiura Y, Yuki D, Wada A, Hino M, Niwa SI, Kondo T, Waki M, Hayasaka T, Masaki N, Akatsu H, Hashizume Y, Yamamoto S, Sato S, Sasaki T, Setou M, Yabe H.
  • Journal Title: Sci Rep. Volume: 7 Issue: 7 Pages: 45050-45050
  • DOI: 10.1038/srep45050
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy. (2017)
  • Author(s): Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T
  • Journal Title: JCI Insight Volume: 2 Issue: 1 Pages: 89462-89478
  • DOI: 10.1172/jci.insight.89462
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histone deacetylase inhibitors inhibit metastasis by restoring a tumor suppressive microRNA-150 in advanced cutaneous T-cell lymphoma. (2017)
  • Author(s): Abe F, Kitadate A, Ikeda S, Yamashita J, Nakanishi H, Takahashi N, Asaka C, Teshima K, Miyagaki T, Sugaya M, Tagawa H.
  • Journal Title: Oncotarget Volume: 8 Issue: 5 Pages: 7572-7585
  • DOI: 10.18632/oncotarget.13810
  • Peer Reviewed / Open Access
• [Journal Article] INPP4B is a PtdIns(3,4,5)P3 phosphatase that can act as a tumor suppressor. (2015)
  • Author(s): Kofuji S, Kimura H, Nakanishi H, Nanjo H, Takasuga S, Liu H, Eguchi S, Nakamura R, Itoh R, Ueno N, Asanuma K, Huang M, Koizumi A, Habuchi T, Yamazaki M, Suzuki A, Sasaki J, Sasaki T
  • Journal Title: Cancer Discovery Volume: in press Issue: 7 Pages: 730-9
  • DOI: 10.1158/2159-8290.cd-14-1329
  • Peer Reviewed / Open Access
• [Journal Article] The role of group IIF secreted phospholipase A2 in epidermal homeostasis and hyperplasia. (2015)
  • Author(s): Yamamoto, K., Miki, Y., Sato, M., Taketomi, Y., Nishito, Y., Taya, C., Muramatsu, K., Ikeda, K., Nakanishi, H., Taguchi, R., Kambe, N., Kabashima, K., Lambeau, G., Gelb, M.H., and Murakami, M
  • Journal Title: J. Exp. Med. Volume: 212 Issue: 11 Pages: 1901-1919
  • DOI: 10.1084/jem.20141904
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ホスホイノシタイドミクス-代謝異常と病態- (2015)
  • Author(s): 中西広樹
  • Journal Title: 実験医学増刊 Volume: 33 Pages: 206-210
• [Book] 生体の科学 (2016)
  • Author(s): 中西広樹
  • Total Pages: 5
  • Publisher: 医学書院
• [Remarks] 秋田大学生体情報研究センター
  • URL: http://www.gipc.akita-u.ac.jp/~arcbs/index.html
• [Patent(Industrial Property Rights)] ホスホイノシタイド分離測定法の開発 (2017)
  • Inventor(s): 中西広樹. 佐々木雄彦. 佐々木純子. 江口賢史. 中西貴代.
  • Industrial Property Rights Holder: 秋田大学, ALTe
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-051354
  • Filing Date: 2017-03-16
• [Patent(Industrial Property Rights)] 新規リン脂質およびその利用. (2016)
  • Inventor(s): 佐々木雄彦. 中西広樹. 江口賢史. 佐々木純子.
  • Industrial Property Rights Holder: 秋田大学, ALTe
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-144177
  • Filing Date: 2016-07-22