Journal of Cellular Biochemistry

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

Authors

  • Loreto Carrasco,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Paola Cea,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Paola Rocco,

    1. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Daniel Peña-Oyarzún,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Pablo Rivera-Mejias,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Cristian Sotomayor-Flores,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Clara Quiroga,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Alfredo Criollo,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Departamento Ciencias Básicas y Comunitarias, Facultad Odontología, Universidad de Chile, Santiago, Chile
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  • Cristian Ibarra,

    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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  • Mario Chiong,

    Corresponding author
    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
    • Correspondence to: Sergio Lavandero or Mario Chiong, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Olivos 1007, Santiago 8380492, Chile.

      E-mail: slavander@uchile.cl or mchiong@uchile.cl

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  • Sergio Lavandero

    Corresponding author
    1. Advanced Center for Chronic Diseases, Universidad de Chile, Santiago, Chile
    2. Centro Estudios Moleculares de la Celula, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Santiago, Chile
    3. Instituto de Ciencias Biomédicas, Facultad Medicina, Universidad de Chile, Santiago, Chile
    4. Cardiology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
    • Correspondence to: Sergio Lavandero or Mario Chiong, Facultad de Ciencias y Farmacéuticas, Universidad de Chile, Olivos 1007, Santiago 8380492, Chile.

      E-mail: slavander@uchile.cl or mchiong@uchile.cl

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  • Conflict of interest: The authors declare no conflicts of interest.

ABSTRACT

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 Gβγ signaling, βARKct. Increases in the activities of Ca2+-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/Ca2+/PKCα/ERK pathway without the participation of calcineurin. J. Cell. Biochem. 115: 712–720, 2014. © 2013 Wiley Periodicals, Inc.

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