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

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 医歯薬学 / シグナル伝達 / 循環器高血圧 / サイクリックAMP / 心不全 / 遺伝子改変マウス / 循環器・高血圧

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
  • NAID: 10031071685
  • Peer Reviewed
• [Journal Article] Pharmacological Stimulation of Type 5 Adenylyl Cyclase Satbilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight (2012)
  • Author(s): Yunzhe Bai, Takashi Tsunematsu, Qibin Jiao, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Meihua Jin, Wenqian Cai, Hui-Ling Jin, Takayuki Fujita, Yasuhiro Ichikawa, Kenji Suita et al.
  • Journal Title: J Pharamacol Sci Volume: 119 Pages: 381-389
  • 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
• [Journal Article] Identification of transcriptional factor E3 (TFE3) as a receptor-independent activator of Gα16 : Gene regulation by nuclear Gα subunit and its activator (2011)
  • Author(s): Sato M., et al.
  • Journal Title: J Biol Chem Volume: (In press)
  • Peer Reviewed
• [Journal Article] Intrarenal suppression of angiotensin II receptor binding molecule in angiotensin II-infused mice (2010)
  • Author(s): Wakui H., et al.
  • Journal Title: Am J Physiol Renal Physiol Volume: 299
  • Peer Reviewed
• [Journal Article] Cardiac-specific activation of angiotensin II type 1 receptor-associated protein completely suppresses cardiac hypertrophy in chronic angiotensin II-infused mice (2010)
  • Author(s): Wakui H., et al.
  • Journal Title: Hypertension Volume: 55 Pages: 1157-1164
  • 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] Disruption of Epac1 protects heart from catecholamine-mediated cardiac fibrosis (2011)
  • Author(s): Satoshi Okumura S, Wenqian Cai, Meihua Jin, Yunzhe Bai, Takashi Tsunematsu, Yuko Hidaka, Reiko Kurotani, Yoshihiro Ishikawa
  • 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(横浜市)
  • 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
• [Presentation] Novel transcription regulation in the hypertrophied myocardium via nuclear Gα16 subunit and activator of G-protein signaling (AGS) (2010)
  • Author(s): Motohiko Sato, Masaharu Hiraoka, Hiroko Suzuki, Bai Yunzhe, Satoshi Okumura, Mary J. Cismowski, Stephen M.Lanier, Yoshihiro Ishikawa
  • Organizer: American Heart Association Scientific Scission 2010
  • Place of Presentation: Chicago in USA
• [Presentation] Disruption of Epac1 Decreases Phosphorylation of Phospholamban and Protects the Heart Against Stress
  • Author(s): Satoshi Okumura, Meihua Jing, Yoshiki Ohnuki, Iyuki Namekata, Reiko Kurotani, Takayuki Fujita, Hui-Ling Jin, Wengian Cai, Yunzhe Bai, Kenji Suita, Takashi Tsunematsu et al.
  • Organizer: American Heart Association Scientific Scission 2012
  • Place of Presentation: Los Angeles, California, USA
• [Presentation] Pharmacological inhibition of STAT3 protect heart from lipopolysaccharide-induced cardiac dysfunction through the inhibition of Jak2/STAT3/iNOS signaling
  • Author(s): Huiling Jin, Satoshi Okumura, Meihua Jin, Wenqian Cai, Kenji Suita, Takashi Tsunematsu, Yunzhe Bai, Takayuki Fujita, Yoshihiro Ishikawa
  • Organizer: The 90 th Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: タワーホール船堀（東京都）
• [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/
• [Remarks] 横浜市立大学大学院医学研究科 循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/
• [Remarks] 横浜市立大学循環制御医学ホームページ
• [Remarks] 横浜市立大学循環制御医学ホームページ