Adachi S, Ito H, Akimoto H, Tanaka M, Fujisaki H, Marumo F, Hiroe M
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
J Mol Cell Cardiol. 1994 Jul;26(7):789-95. doi: 10.1006/jmcc.1994.1096.
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.
在本研究中，我们检测了胰岛素样生长因子-II（IGF-II）是否能诱导培养的新生大鼠心肌细胞肥大。IGF-II（10^(-7) M）作用48小时后增加了心肌细胞的表面积和蛋白含量。通过[3H]亮氨酸掺入法评估，IGF-II呈剂量依赖性（10^(-10)-10^(-7) M）刺激蛋白合成；在10^(-7) M时最大反应比对照增加1.7倍。由于心肌肥大的反应特征是肌肉特异性基因表达增强，通过Northern印迹分析评估了IGF-II对肌球蛋白轻链2（MLC2）、肌钙蛋白I和α-肌动蛋白异构体（骨骼肌和心肌异构体）mRNA稳态水平的影响。IGF-II（10^(-7) M）早在60分钟时就增加了MLC2、肌钙蛋白I和骨骼肌α-肌动蛋白的mRNA水平，6小时后达到最大反应，而心肌α-肌动蛋白mRNA水平未受影响。钙通道阻滞剂尼卡地平抑制了IGF-II刺激的骨骼肌α-肌动蛋白mRNA水平，然而，蛋白激酶C抑制剂H-7则没有影响。这些结果表明IGF-II在心肌肥大中发挥潜在作用。
