Hypertrophic effects of urocortin homologous peptides are mediated via activation of the Akt pathway.
The UCN homologues SCP and SRP bind specifically to the CRFR2 receptor, whereas UCN binds to both CRFR1 and CRFR2. We have previously demonstrated that all three peptides are cardioprotective, and both the Akt and MAPK p42/44 pathways are essential for this effect. Here we tested the hypertrophic effects of these peptides. We examined the effects of the peptides on cell area, protein synthesis, and induction of the natriuretic peptides ANP and BNP. All three peptides were able to increase all the markers of hypertrophy examined, with SCP being the most potent of the three, followed by UCN and SRP last. In addition, we provide a mechanism of action for the three peptides and show that Akt phosphorylation is important for their hypertrophic action, whereas MAPK p42/44 is not involved in this effect.
Chanalaris
Anastasios
A
Medical Molecular Biology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK. A.Chanalaris@ich.ucl.ac.uk
Lawrence
Kevin M
KM
Townsend
Paul A
PA
Davidson
Sean
S
Jamshidi
Yalda
Y
Jashmidi
Yalda
Y
Stephanou
Anastasis
A
Knight
Richard D
RD
Hsu
Sheau Y
SY
Hsueh
Aaron J W
AJ
Latchman
David S
DS
D000818:Animals; D000831:Animals, Newborn; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D054832:Urocortins
D011518:Proto-Oncogene Proteins; C426705:UCN2 protein, human; C426704:UCN3 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt