Role of ischemia-inducible activator of G-protein signaling in cellular response to pathophysiological stimuli

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Aichi Medical University
• Principal Investigator: SATO Motohiko 愛知医科大学, 医学部, 教授 (40292122)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Naoki 愛知医科大学, 医学部, 講師 (40278362) ; SATO Maki 愛知医科大学, 医学部, 助教 (60351102)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: シグナル伝達 / Ｇ蛋白質 / 心筋保護 / 循環器病学

Outline of Final Research Achievements

We previously identified an ischemia-inducible G-protein activator, activator of G-protein signaling 8 (AGS8), which interacts directly with Gβγ and regulated a critical cascade leading apoptosis of cardiomyocyte under hypoxia. We tried to protect cardiomyocytes from hypoxic injury by disrupting AGS8 mediated Gβγ-singling. We developed a peptide (AGS8-peptide) that blocked the association of Gβγ with AGS8 based on amino acid sequences of the Gβγ binding domain of AGS8. AGS8-peptide successfully blocked the interaction of Gβγ with AGS8 in vitro. To evaluate effect of AGS8-peptide in vivo, rat neonatal cardiomyocytes were exposed to hypoxia (6 h)/reoxygenation (18 h). AGS8-peptide was successfully transferred to cardiomyocytes, and blocked apoptosis of cardiomyocytes. These data indicated an importance of AGS8 mediated Gβγ-signaling in apoptosis of cardiomyocytes, and its potential as novel therapeutic target.

Free Research Field

生理学