Adenoviral Gene Transfer of Activated Phosphatidylinositol 3′-Kinase and Akt Inhibits Apoptosis of Hypoxic Cardiomyocytes In Vitro

• DOI: 10.1161/01.cir.100.23.2373
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Takashi Matsui; Ling Li; Federica del Monte; Yasuhisa Fukui; Thomas F. Franke; Roger J. Hajjar; Anthony Rosenzweig
• Keywords: DNA laddering

Background —The intracellular signaling pathways that control cardiomyocyte apoptosis have not been fully defined. Because insulin-like growth factor-1 (IGF-1) prevents apoptosis, we examined the role of its downstream molecules in an vitro model hypoxia-induced apoptosis. Methods and Results —Treatment rat neonatal cardiomyocytes with IGF-1 increased activity both phosphatidylinositol 3′ (PI 3)-kinase target, Akt (also known as protein kinase B or PKB). Cardiomyocytes were subjected to hypoxia for 24 hours, was assessed by DNA laddering, TUNEL staining, ELISA histone-associated fragments. treatment (100 nmol/L) reduced this effect inhibited simultaneous a PI 3-kinase inhibitor. infected either adenovirus (Ad.EGFP) adenoviruses carrying constitutively active forms (Ad.BD110) (Ad.myr-Akt-HA). Ad.BD110 significantly hypoxic compared Ad.EGFP (61.0±4.6% less fragmentation than Ad.EGFP-infected cells, P <0.0001). Ad.myr-Akt-HA even more dramatically (90.9±1.4% controls, Conclusions —IGF-1 activates cardiomyocytes. Activated are each sufficient protect against vitro. Adenoviral gene transfer provides useful tool investigating these