Cardiac hormones activate ERK 1/2 kinases in human fibroblasts.
Two cardiac hormones, vessel dilator and kaliuretic peptide, localize to fibroblasts with immunohistochemistry. Vessel dilator and kaliuretic peptide were investigated in dose-response and time-sequenced experiments for their cell signaling of extracellular signal-regulated kinases 1/2 in human fibroblasts to test the hypothesis that these two cardiovascular hormones contribute to fibroblast proliferation by activating extracellular signal-regulated kinases 1/2. Vessel dilator at 10 pM (physiological range) enhanced the phosphorylation of extracellular signal-regulated kinases 1/2 by 188+/-9% (p<0.001) in 10 min and, maximally, by 200+/-10% in 15 min (p<0.001). Vessel dilator at 10 nM enhanced the phosphorylation of extracellular signal-regulated kinases 1/2 by 107+/-5% (p<0.01) in 10 min. Kaliuretic peptide at 10 pM enhanced the activation of extracellular signal-regulated kinases 1/2 by 389+/-19% in 10 min (p<0.001). Kaliuretic peptide at 10 nM enhanced the phosphorylation of extracellular signal-regulated kinases 1/2 by 82+/-4% (p<0.01). Our results show that both cardiac hormones activate extracellular signal-regulated kinases 1/2 in human fibroblasts, suggesting that they may have a role in enhancing fibroblast proliferation.
Department of Internal Medicine, Molecular Pharmacology and Physiology, James A. Haley Veterans Medical Center and University of South Florida Cardiac Hormone Center, Tampa, Florida 33612, USA.
Y
Y
Sun
E J
EJ
Eichelbaum
H
H
Wang
D L
DL
Vesely
D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects*; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D000254:Sodium-Potassium-Exchanging ATPase