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.
Sun
Y
Y
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.
Eichelbaum
E J
EJ
Wang
H
H
Vesely
D L
DL
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