Systematic survey for novel cardiovascular peptides in porcine atrium

• Project/Area Number: 16K15446
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: University of Miyazaki
• Principal Investigator: Kitamura Kazuo 宮崎大学, 医学部, 教授 (50204912)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 生理活性ペプチド / cAMP / アミド化 / アンジオテンシン / バイオマーカー

Outline of Final Research Achievements

We searched for cardiovascular peptides in peptide extract from 1kg of porcine atrium using three assay systems established by us. (1) The assay that elevates platelet cAMP: We isolated several biologically active peptides which derived from vasoactive intestinal peptide (VIP) and calcitonin gene related peptide (CGRP). (2) Assay for the peptide with C-terminal amide structure: We discovered three novel endogenous peptides with C-terminal amide structure, but their biological activities are unknown. (3) Search for angiotensin related peptide: We isolated several angiotensin related peptides which are very little and considered to be metabolites of angiotensin.

Academic Significance and Societal Importance of the Research Achievements

わが国ではナトリウム利尿ペプチドやエンドセリン（ET）、アドレノメデュリン（AM）、グレリン等が相次いで発見され、新たな生体内調節機構の存在が明らかにされてきた。複雑で精巧な生体のメカニズムやその異常により引き起こされる疾患の病態解明には、未だ同定されていない生理活性物質の存在を明らかにして構造を決定することが重要である。また、これらのペプチドのいくつかは診断薬や治療薬として臨床応用されており、医療の発展を通じて社会に貢献できている。本研究では、ブタ心房組織より新しい生理活性ペプチドの発見を目指す真に独創的で先駆的な研究であり、医療の発展にも貢献できる可能性がある。

Research Products

• [Journal Article] Developments of human adrenomedullin-IgG1 Fc fusion proteins. J (2019)
  • Author(s): Nagata S, Yamasaki M, Kawano A, Kitamura K
  • Journal Title: Biochem Volume: 78 Issue: 2 Pages: 129-134
  • DOI: 10.1093/jb/mvz023
  • Peer Reviewed / Open Access
• [Journal Article] Adrenomedullin: Continuing to explore cardioprotection. (2018)
  • Author(s): Tsuruda T, Kato J, Kuwasako K, Kitamura K
  • Journal Title: Peptides Volume: in press Pages: 47-54
  • DOI: 10.1016/j.peptides.2018.03.012
  • Peer Reviewed / Open Access
• [Journal Article] Anti-Inflammatory Effects of PEGylated Human Adrenomedullin in a Mouse DSS-Induced Colitis Model. (2017)
  • Author(s): Sayaka Nagata, Motoo Yamasaki, Kazuo Kitamura
  • Journal Title: Drug Development Research Volume: in press Issue: 3-4 Pages: 129-134
  • DOI: 10.1002/ddr.21383
  • Peer Reviewed / Open Access
• [Journal Article] Beta-arrestins negatively control human adrenomedullin type 1-receptor internalization. (2017)
  • Author(s): Kuwasako K, Kitamura K, Nagata S, Sekiguchi T, Jiang D, Murakami N, Hattori Y, Kato J
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中 Issue: 2 Pages: 438-443
  • DOI: 10.1016/j.bbrc.2017.04.083
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] アドレノメデュリンと関連ペプチドの疾患マーカーとしての意義 (2016)
  • Author(s): 北村和雄
  • Journal Title: 生体の化学 Volume: 67（5） Pages: 434-435
  • Peer Reviewed
• [Presentation] アドレノメデュリンのトランスレーショナルリサーチ (2018)
  • Author(s): 北村和雄
  • Organizer: 第39回日本循環制御医学会総会
• [Presentation] Big angiotensin-25: a novel component of the renin angiotensin system. (2018)
  • Author(s): Nagata S, Kitamura K
  • Organizer: Angiotensin Gordon Research Conference.
  • Int'l Joint Research
• [Presentation] Anti-inflammatory effects of PEGylated human adrenomedullin on DSS-induced colitis in mice. (2018)
  • Author(s): Nagata S, Yamasaki M, Kitamura K
  • Organizer: CGRP Family Peptides Conference 2018.
  • Int'l Joint Research
• [Presentation] The translational research of adrenomedullin: Adrenomedullin as a potential therapeutic agent for ulcerative colitis (2017)
  • Author(s): Kitamura K
  • Organizer: The 2nd International Conference on Internal Medicine & Hospital Medicine
  • Int'l Joint Research
• [Presentation] 持続性アドレノメデュリン誘導体の創製 (2017)
  • Author(s): 永田さやか, 山﨑基生, 北村和雄
  • Organizer: 第21回日本心血管内分泌代謝学会学術総会
• [Presentation] 炎症性腸疾患におけるアドレノメデュリン療法の開発 (2017)
  • Author(s): 芦塚伸也
  • Organizer: 第18回宮崎IBD講演会
• [Presentation] 組織アンジオテンシンⅡ生成における新規ペプチドの単離 (2016)
  • Author(s): 永田さやか、北村和雄
  • Organizer: 日本動物学会第87回沖縄大会
  • Place of Presentation: 沖縄県宜野湾市
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Biochemical properties of the N-terminally palmitoyated adrenomedullin. (2016)
  • Author(s): Tokashiki M, Kubo K, Kuwasako K, Nagata S, Kato J, Kitamura K.
  • Organizer: The 26th Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene. (2016)
  • Author(s): Tsuruda T, Hao Y, Kurogi S, Nakamura M, Udagawa N, Chosa E, Asada Y, Kitamura K:
  • Organizer: American College of Cardiology. Geriatric Cardiology Section Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research