G-protein activation and expression in lung injury

Lung injury and repair are characterized by changes in the phenotypic and functional characteristics of parenchymal cells. It is not known to what extent these changes are regulated by alterations in total G-protein activity or expression of G-protein subfamilies. G-proteins (GTPases) are receptor-associated proteins that act as molecular switches for signal transduction pathways. They are involved in regulating ribosomal protein synthesis, transmembrane signaling of hormones and growth factors, cellular differentiation and proliferation and guiding organelle movement within cells. In this study, we validated, modified and optimized the experimental conditions needed to evaluate GTPase activity in the lung. We also measured changes in GTPase activity and the expression of G-protein subfamilies in lungs undergoing paraquat lung injury. Total GTPase activity as well as the expression of Gi, Gs, and Go subfamilies demonstrated a sharp increase on day 1 after injury, a time previously shown to coincide with rapid cellular proliferation and increased protein synthesis. In contrast to the other subfamilies, expression of the alpha subunit of the Gs subfamily was more intense and sustained during the repair phase (day 14). These findings implicate G-proteins in general, and the Gs subfamily, in particular, in regulating cellular function during lung repair.