Artículos de revistas
Role of heterotrimeric G protein and calcium in cardiomyocyte hypertrophy induced by IGF-1
Fecha
2014Registro en:
Journal of Cellular Biochemistry 115:712–720 (2014)
10974644
07302312
10.1002/jcb.24712
Autor
Carrasco Mujica, Loreto
Cea, Paola
Rocco, Paola
Peña Oyarzún, Daniel
Rivera Mejías, Pablo
Sotomayor Flores, Cristian Alejandro
Quiroga, Clara
Criollo Céspedes, Alfredo
Ibarra, Cristián
Chiong Lay, Mario
Lavandero González, Sergio
Institución
Resumen
In the heart, insulin‐like growth factor‐1 (IGF‐1) is a peptide with pro‐hypertrophic and anti‐apoptotic actions. The pro‐hypertrophic properties
of IGF‐1 have been attributed to the extracellular regulated kinase (ERK) pathway. Recently, we reported that IGF‐1 also increases intracellular
Ca2þ levels through a pertussis toxin (PTX)‐sensitive G protein. Here we investigate whether this Ca2þ signal is involved in IGF‐1‐induced
cardiomyocyte hypertrophy. Our results show that the IGF‐1‐induced increase in Ca2þ level is abolished by the IGF‐1 receptor tyrosine kinase
inhibitor AG538, PTX and the peptide inhibitor of Gbg signaling, bARKct. Increases in the activities of Ca2þ‐dependent enzymes calcineurin,
calmodulin kinase II (CaMKII), and protein kinase Ca (PKCa) were observed at 5 min after IGF‐1 exposure. AG538, PTX, bARKct, and the
dominant negative PKCa prevented the IGF‐1‐dependent phosphorylation of ERK1/2. Participation of calcineurin and CaMKII in ERK
phosphorylation was discounted. IGF‐1‐induced cardiomyocyte hypertrophy, determined by cell size and b‐myosin heavy chain (b‐MHC), was
prevented by AG538, PTX, bARKct, dominant negative PKCa, and the MEK1/2 inhibitor PD98059. Inhibition of calcineurin with CAIN did not
abolish IGF‐1‐induced cardiac hypertrophy. We conclude that IGF‐1 induces hypertrophy in cultured cardiomyocytes by activation of the
receptor tyrosine kinase activity/bg‐subunits of a PTX‐sensitive G protein/Ca2þ/PKCa/ERK pathway without the participation of calcineurin.