Towards drug development based on molecular interactions involving growth hormone

• Project/Area Number: 24791518
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Teikyo Heisei University
• Principal Investigator: MIZUTANI Akiko 帝京平成大学, 健康メディカル学部, 講師 (80465252)
• Co-Investigator(Renkei-kenkyūsha): MATSUNO AKIRA 帝京大学, 医学部, 教授 (00242058)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 相互作用 / 成長ホルモン / 分泌 / 細胞内局在 / 下垂体

Outline of Final Research Achievements

We identified dozens of novel interactor candidates of human growth hormone (GH) using our improved yeast two-hybrid method, and focused our efforts on the analyses of one of them, referred to here as “protein X”. We first confirmed that protein X is important for GH secretion in cells. We further found that protein X, expressed in E. coli, can interact with GH in vitro. The region containing the GH interaction surface of protein X was delineated within a 93-aa region. It has been reported that protein X can also interact with other hormones than GH, but our mutational analyses have revealed that the structure of protein-X interaction surface for GH is different from those for other hormones. The results therefore could provide a basis for designing inhibitor peptides that specifically deteriorate the GH-protein X interaction.

Research Products

• [Journal Article] Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membrane in MDCK II cells. (2014)
  • Author(s): Kagawa T, Orii R, Hirose S, Arase Y, Shiraishi K, Mizutani A, Tsukamoto H, Mine T.
  • Journal Title: J Gastroenterol Volume: 49 Issue: 5 Pages: 890-899
  • DOI: 10.1007/s00535-013-0833-y
  • Peer Reviewed
• [Journal Article] Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese (2014)
  • Author(s): Matsuzaka Y, Ohkubo T, Kikuti YY, Mizutani A, Tsuda M, Aoyama Y, Kakuta K, Oka A, Inoko H, Sakabe K, Ishikawa S, Kulski JK, Kimura M
  • Journal Title: Environ Toxicol Volume: 29 Pages: 1217-1226
  • Peer Reviewed
• [Journal Article] Subarachnoid hemorrhage secondary to a ruptured middle cerebral aneurysm in a patient with osteogenesis imperfecta: a case report (2014)
  • Author(s): Hirohata T, Miyawaki S, Mizutani A, Iwakami T, Yamada S, Nishido H, Suzuki Y, Miyamoto S, Hoya K, Murakami M, Matsuno A
  • Journal Title: BMC Neurol Volume: 23
  • Peer Reviewed / Open Access
• [Journal Article] Modified S/MAR episomal vectors for stably expressing fluorescent protein-tagged transgenes with small cell-to-cell fluctuations (2013)
  • Author(s): Mizutani A, Kikkawa E, Matsuno A, Tanaka M, Inoko H
  • Journal Title: Analytical Biochemistry Volume: 443 Pages: 113-116
  • Peer Reviewed
• [Journal Article] Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency (2013)
  • Author(s): Hirohata T, Saito N, Takano K, Yamada S, Son JH, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Mizutani A, Okinaga H, Matsuno A
  • Journal Title: Endocr J Volume: 60 Pages: 369-373
  • NAID: 10031170622
  • Peer Reviewed
• [Journal Article] Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency (2012)
  • Author(s): Hirohata T., et.al.
  • Journal Title: Endocr J Volume: 60 Pages: 369-373
  • Peer Reviewed
• [Presentation] ヒト成長ホルモンと、その選別輸送・分泌に関わる因子として新規に同定したCPEの相互作用の検討 (2015)
  • Author(s): 水谷 晃子
  • Organizer: 日本生化学会日本分子生物学会合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 外来性遺伝子の安定発現細胞株の確立に適したS/MARエピソームベクターの構築 (2014)
  • Author(s): 水谷 晃子
  • Organizer: 日本生化学会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Identification of a novel interactor of human growth hormone (2012)
  • Author(s): Mizutani A
  • Organizer: 14th International Congress of Histochemistry and Cytochemistry
  • Place of Presentation: 京都国際会議場（京都）
• [Presentation] ヒト成長ホルモンの新規相互作用因子の機能解析 (2012)
  • Author(s): 水谷 晃子
  • Organizer: 第85回日本生化学会
  • Place of Presentation: マリンメッセ福岡（福岡）