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-protein-coupled receptor (GPCR) signaling. Sepsis is a pathophysiological condition that is induced primarily in response to bacterial infection and is associated with decreased responsiveness to a number of vasoactive GPCR agonists. Using a degenerate RT-PCR screen, we report that RGS1 and RGS16 were amplified from the heart and aorta of septic animals. By Northern blot analysis, RGS1 and RGS16 were upregulated, with their respective levels increasing 6- and 50-fold in septic hearts. Using a yeast-based bioassay, both RGS1 and RGS16 were found to be equipotent in their ability to attenuate GPCR signaling. These results suggest that both RGS1 and RGS16 contribute to the sepsis-mediated decrease in GPCR signaling. Elevated levels of some RGSs may also lead to an increase in Gbetagamma-activated signaling pathways in the absence of GPCR agonists. Using a c-fos luciferase reporter gene that is responsive to Gbetagamma-activated signaling pathways, we observed a respective 8- and 7-fold increase in the basal luciferase in serum-deprived transfected mammalian cells overexpressing RGS1 or RGS16. This suggests that RGSs play a role in promoting the sepsis-mediated increases in the activation of intracellular signal transduction pathways.
Panetta
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Department of Medicine and Anatomy, McGill University and the Royal Victoria Hospital, Montreal, Quebec, H3A 1A1, Canada.
Guo
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Y
Magder
S
S
Greenwood
M T
MT
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D016762:Genes, fos; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D020710:RGS Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013552:Swine; D014162:Transfection
D008070:Lipopolysaccharides; D011506:Proteins; D020710:RGS Proteins; C107413:RGS16 protein