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Role of Heterotrimeric G Protein and Calcium in Cardiomyocyte Hypertrophy Induced by IGF‐1
Author(s) -
Carrasco Loreto,
Cea Paola,
Rocco Paola,
PeñaOyarzún Daniel,
RiveraMejias Pablo,
SotomayorFlores Cristian,
Quiroga Clara,
Criollo Alfredo,
Ibarra Cristian,
Chiong Mario,
Lavandero Sergio
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24712
Subject(s) - calcineurin , protein kinase c , mapk/erk pathway , medicine , endocrinology , kinase , protein kinase a , tyrosine phosphorylation , biology , signal transduction , phosphorylation , microbiology and biotechnology , tyrosine kinase , transplantation
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 Ca 2+ levels through a pertussis toxin (PTX)‐sensitive G protein. Here we investigate whether this Ca 2+ signal is involved in IGF‐1‐induced cardiomyocyte hypertrophy. Our results show that the IGF‐1‐induced increase in Ca 2+ level is abolished by the IGF‐1 receptor tyrosine kinase inhibitor AG538, PTX and the peptide inhibitor of Gβγ signaling, βARKct. Increases in the activities of Ca 2+ ‐dependent enzymes calcineurin, calmodulin kinase II (CaMKII), and protein kinase Cα (PKCα) were observed at 5 min after IGF‐1 exposure. AG538, PTX, βARKct, and the dominant negative PKCα 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 β‐myosin heavy chain (β‐MHC), was prevented by AG538, PTX, βARKct, dominant negative PKCα, 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/βγ‐subunits of a PTX‐sensitive G protein/Ca 2+ /PKCα/ERK pathway without the participation of calcineurin. J. Cell. Biochem. 115: 712–720, 2014. © 2013 Wiley Periodicals, Inc.