Insulin-like growth factor-II induces hypertrophy with increased expression of muscle specific genes in cultured rat cardiomyocytes

Abstract

In the present study, we examined whether insulin-like growth factor-II (IGF-II) induces hypertrophy of cultured neonatal rat cardiomyocytes. IGF-II (10(-7) M) increased the cell surface area of, and the protein content in, cardiomyocytes after 48 h-exposure. IGF-II dose-dependently (10(-10)-10(-7) M) stimulated protein synthesis as evaluated by [3H]leucine incorporation; the maximum response was 1.7-fold increase over control at 10(-7) M. Since the response of cardiac hypertrophy is characterized by enhanced expression of muscle specific genes, effects of IGF-II on steady-state levels of mRNA for myosin light chain 2 (MLC2), troponin I and alpha-actin isoforms (skeletal and cardiac isoforms) were evaluated by Northern blot analysis. IGF-II (10(-7) M) increased mRNA levels for MLC2, troponin I and skeletal alpha-actin, as early as 60 min with a maximum response after 6 h, whereas cardiac alpha-actin mRNA levels were unaffected. Calcium channel blocker, nicardipine, inhibited IGF-II-stimulated skeletal alpha-actin mRNA levels, however, inhibitor of protein kinase C, H-7, unaffected. These results suggest that IGF-II plays a potential role in cardiac hypertrophy.