Analysis of type 5 adenylyl cyclase role for the production of active oxygen and its clinical application for the treatment of heart failure

2012 Fiscal Year Final Research Report

• Project/Area Number: 22790719
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: BAI Yunzhe 横浜市立大学, 医学研究科, 共同研究員 (50571147)
• Project Period (FY): 2010 – 2012
• Keywords: 医歯薬学

Research Abstract

Type 5 adenylyl cyclase (AC5)is a major cardiac isoform and AC5 null mice show the resistance to oxidative stress and heart failure. Recent studies have shown that cAMP can activate Epac1, exchange protein directly activated by cAMP, as well. However, its role in the pathogenesis of heart failure remains unknown. In order to examine the role of Epac1 in the heart, we have generated the cardiac-specific type 5 adenylyl cyclase, a major cardiac AC isoform, transgenic mice (AC5TG) and Epac1-deficient AC5TG (AC5TG-EpacKO) and demonstrated that cAMP-Epac1 pathway plays an important role for the development of heart failure through the activation of cAMP-PKA pathway, suggesting that this pathway may be a new target for the treatment of heart failure.

Research Products

• [Journal Article] Pharmacological stimulation of type 5 adenylyl cyclase stabilizes heart rate under both microgravity and hypergravity induced by parabolic flight (2012)
  • Author(s): Bai Y, Tsunematsu T, Jiao Q, Ohnuki Y, Mototani Y, Shiozawa K, Jin M, Cai W, Jin HL, Fujita T, Ichikawa Y, Suita K, Kurotani R, Yokoyama U, Sato M, Iwatsubo K, Ishikawa Y, Okumura S
  • Journal Title: J Pharmacol Sci Volume: 119:381-189
  • Peer Reviewed
• [Journal Article] Sato M, Hiraoka M, Suzuki H, Bai Y, Kurotani R, Yokoyama U, Okumura S, Cismowski MJ, Lanier SM, Ishikawa Y (2011)
  • Author(s): Sato M, Hiraoka M, Suzuki H, Bai Y, Kurotani R, Yokoyama U, Okumura S, Cismowski MJ, Lanier SM, Ishikawa Y
  • Journal Title: J Biol Chem Volume: 286 Pages: 17766-17776
  • Peer Reviewed
• [Presentation] Tsunematsu T, Fujita T,Ishikawa I Pharmacological inhibition of STAT3 protect heart from lipopolysaccharide-induced cardiac dysfunction through the inhibition of Jak2/STAT3/iNOS signaling (2013)
  • Author(s): Jin H-L, Okumura S, Jin M, Cai W, Suita K, Bai Y
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀,(東京都)
  • Year and Date: 2013-03-28
• [Presentation] Disruption of Epac1 decreases phosphorylation of phospholamban and protects the heart against stress (2012)
  • Author(s): Okumura S, Jing M, Ohnuki Y, Namekata I, Kurotani R, Fujita T, Jin H-L, Cai W, Bai Y, Suita K, Tsunematsu T et al
  • Organizer: merican Heart Association Scientific Scission 2012
  • Place of Presentation: Los Angeles, California, USA
  • Year and Date: 2012-11-06
• [Presentation] Epac activation protects heart from interleukin-6-induced cardiac dysfunction by inhibiting STAT/iNOS signaling (2011)
  • Author(s): Okumura S, Jin M, Kawamata F, Jin H-L, Cai W, Bai Y, Suita K, Hidaka Y, Tsunematsu T, Ishikawa Y
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando in USA
  • Year and Date: 2011-11-14
• [Presentation] Disruption of Epac1 Protects Heart from Catecholamine-mediated Cardiac Fibrosis (2011)
  • Author(s): Okumura S, Cai W, Jin M, Bai Y, Tsunematsu T, HidakaY, Kurotani R, Ishikawa Y
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-08-03
• [Presentation] Novel transcription regulation in the hypertrophied myocardium via nuclear G 16 subunit and activator of G-protein signaling (AGS) (2010)
  • Author(s): Sato M, Hiraoka M, Suzuki H, Bai Y, Okumura S, Cismowski MJ, Lanier, SM, Ishikawa Y
  • Organizer: American Heart Association Scientific Sessions 2010
  • Place of Presentation: Chicago in USA
  • Year and Date: 2010-11-16
• [Remarks] 横浜市立大学循環制御医学 ホームページ
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/