抄録
Recently, we identified a novel receptor-independent G-protein activator, Activator of G-protein signaling 8 (AGS8), from cDNA library of rat hearts subjected to repetitive transient ischemia. AGS8 was induced in the ischemic myocardium and regulated Gβγ signaling. In face of myocardial ischemia and/or ischemia/reperfusion, AGS8 would provide an additional signal input responsible for myocardial adaptation, however the nature of this protein has not been characterized. As an initial step to investigate physiological roles of AGS8, we examined an impact of AGS8 on hypoxia-induced apoptosis in cardiomyocyte and its subcellular localization. Cultured rat neonatal cardiomyocyte (NCM) were exposed to hypoxia for 6, 24 hr or hypoxia (6hr)/reoxygenation (18hr) following treatment of siRNA for AGS8. Apoptosis of cells were determined by DNA end-labeling, annexin V, and/or mitochondrial membrane potential. Surprisingly, silencing of AGS8 inhibited apoptosis of cardiomyocyte induced by hypoxia alone as well as hypoxia/reoxygenation. Antibody against AGS8 recognized immunoreactive signals that enriched at cell-cell interface. These data suggested that AGS8 was involved in the formation of apoptotic signaling induced by hypoxia and that AGS8-enriched spots might be contributed to an integration of such signals. An effective inhibition of apoptosis by siRNA for AGS8 implies a potential of therapeutic target to protect the myocardium from ischemic events. [J Physiol Sci. 2008;58 Suppl:S206]
