Identification of a novel G-protein activator induced by cardiac ischemia/hypoxia

Abstract

Recent data indicate the existence of accessory proteins that directly regulate the activation status of heterotrimeric G-protein, which may serve additional regulatory points for cellular events. We asked if they were involved in an adaptation of myocardium to ischemia. A cDNA library was generated from rat hearts subjected to repetitive transient ischemia that was induced by inflation of an implanted balloon around the coronary artery. Utilizing a functional screen in yeast for G-protein activators, we isolated a novel G-protein activator (AGS8). AGS8 mRNA was induced in response to ventricular ischemia but not by tachycardia, hypertrophy or cardiac failure. Hypoxia induced AGS8 mRNA in isolated adult ventricular cardiomyocytes but not other cell types suggesting a myocyte specific adaptation mechanism involving remodeling of G-protein signaling pathways. Subsequent studies indicated that AGS8 interacts directly with Gβγ and this occurs in a manner that apparently does not alter the regulation of the effector PLC-β2 by Gβγ. These data indicate that AGS8 provides an alternative signal input to G-proteins independent of receptors. Such mechanisms may provide an important role in the adaptation of the myocardium to ischemia. [J Physiol Sci. 2007;57 Suppl:S85]