Abstract 226: GGF2 Requires Activation Of PI3 Kinase Pathway To Mediate Cytoprotective Effects In The Mouse Atrial-derived Hl-1 Cardiomyocyte-like Cell Line

Glial growth factor (GGF2) is a Neuregulin-1 (NRG-1), which binds ErbB receptors and activates downstream cell signaling processes. NRG-1 ligands and their receptors are required for cardiac development and adult cardiac function. GGF2 has been shown to improve left ventricular function in several models of heart failure though the mechanisms by which GGF2 is efficacious are poorly understood. GGF2 is currently in clinical trials for treatment of congestive heart failure. Many studies have focused on GGF2 regulation of PI3 kinase (PI3K) as measured by formation of pAKT in vivo and in numerous cell lines, including HL-1 cells, neonatal rat ventricular myocytes (NRVMs) and human iPSC-derived cardiomyocytes. NRG-1s also activate the MAP kinase (MAPK) pathway as measured by pERK1/2 formation. To better understand GGF2 action in the stressed heart, we have developed in vitro systems to study GGF2 protection of cardiomyocytes from doxorubicin induced toxicity. After serum starvation, cells were pre-incubated wi...