Regulators of G-protein signaling (RGS) 1 and 16 are induced in response to bacterial lipopolysaccharide and stimulate c-fos promoter expression

Regulators of G-protein signaling (RGS) are negative regulators of G-protei n-coupled receptor (GPCR) signaling. Sepsis is a pathophysiological conditi on that is induced primarily in response to bacterial infection and is asso ciated with decreased responsiveness to a number of vasoactive GPCR agonist s. Using a degenerate RT-PCR screen, we report that RGS1 and RGS16 were amp lified from the heart and aorta of septic animals. By Northern blot analysi s, RGS1 and RGS16 were upregulated, with their respective levels increasing 6- and 50-fold in septic hearts. Using a yeast-based bioassay, both RGS1 a nd RGS16 were found to be equipotent in their ability to attenuate GPCR sig naling. These results suggest that both RGS1 and RGS16 contribute to the se psis-mediated decrease in GPCR signaling. Elevated levels of some RGSs may also lead to an increase in G(beta gamma)-activated signaling pathways in t he absence of GPCR agonists. Using a c-fos luciferase reporter gene that is responsive to G(beta gamma)-activated signaling pathways, we observed a re spective 8- and 7-fold increase in the basal luciferase in serum-deprived t ransfected mammalian cells overexpressing RGS1 or RGS16. This suggests that RGSs play a role in promoting the sepsis-mediated increases in the activat ion of intracellular signal transduction pathways. (C) 1999 Academic Press.