Abstract 9901: Cardiac Protection From Hypoxic Injury by a Novel Synthetic Peptide Targeting the Activator of G-Protein Signaling 8-Mediated Gβγ Signal

Ischemia-reperfusion injury of the heart is associated with activation of multiple signaling pathways including those of heterotrimeric G-protein. We identified an ischemia-inducible G-protein activator, activator of G-protein signaling 8 (AGS8), which interacts directly with Gβγ and regulates Gβγ signaling in cells. The knockdown of AGS8 by siRNA dramatically blocked hypoxia-induced apoptosis of cardiomyocytes, suggesting AGS8 triggered a critical cascade leading to cell death, which could be a novel therapeutic target. To investigate this possibility further, we attempted to protect cardiomyocytes from hypoxia-induced apoptosis by utilizing a synthetic peptide which disrupts AGS8-mediated Gβγ signaling. We first 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. We then investigated the effects of the AGS8-peptide on cardiomyocytes exposed to hypoxic stress. Cultured rat neonatal cardiomyocytes were exposed to...