Role of Heterotrimeric G Protein and Calcium in Cardiomyocyte Hypertrophy Induced by IGF-1

CARRASCO L.; Cea, P; Rocco, P; Pena-Oyarzun, D; Rivera-Mejias, P; Sotomayor-Flores, C; Quiroga, C; Criollo, A; Ibarra, C; Chiong M.; Lavandero S.


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 Ca2+ levels through a pertussis toxin (PTX)-sensitive G protein. Here we investigate whether this Ca2+ signal is involved in IGF-1-induced cardiomyocyte hypertrophy. Our results show that the IGF-1-induced increase in Ca2+ level is abolished by the IGF-1 receptor tyrosine kinase inhibitor AG538, PTX and the peptide inhibitor of G signaling, ARKct. Increases in the activities of Ca2+-dependent enzymes calcineurin, calmodulin kinase II (CaMKII), and protein kinase C (PKC) were observed at 5min after IGF-1 exposure. AG538, PTX, ARKct, and the dominant negative PKC 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 -myosin heavy chain (-MHC), was prevented by AG538, PTX, ARKct, dominant negative PKC, 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/-subunits of a PTX-sensitive G protein/Ca2+/PKC/ERK pathway without the participation of calcineurin. J. Cell. Biochem. 115: 712-720, 2014. (c) 2013 Wiley Periodicals, Inc.

Más información

Título según WOS: Role of Heterotrimeric G Protein and Calcium in Cardiomyocyte Hypertrophy Induced by IGF-1
Título según SCOPUS: Role of heterotrimeric G protein and calcium in cardiomyocyte hypertrophy induced by IGF-1
Volumen: 115
Número: 4
Editorial: Wiley
Fecha de publicación: 2014
Página de inicio: 712
Página final: 720
Idioma: English