Matsui T, Yamaguchi M
Laboratory of Metabolism and Endocrinology, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
Peptides. 1995;16(6):1063-8. doi: 10.1016/0196-9781(95)00067-t.
Whether the anabolic effect of insulin-like growth factor-I (IGF-I) in osteoblastic MC3T3-E1 cells is modulated by zinc, an activator of bone formation, was investigated in vitro. After subculture for 3 days, the cells were cultured for 72 h with IGF-I (10(-8) M). The peptide produced a significant increase of protein concentration, deoxyribonucleic acid (DNA) content, and cell number in the cells. These increases were markedly enhanced by the presence of zinc sulfate (10(-5) M), but not zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-5) M). Also, the cellular alkaline phosphatase activity was synergistically increased by the presence of both IGF-I and zinc sulfate. Thus, effect was not seen in the presence of both insulin (10(-8) M) and zinc sulfate (10(-5) M). The effect of zinc sulfate to enhance the IGF-I-increased alkaline phosphatase activity and protein concentration in the cells was clearly prevented by the presence of cycloheximide (10(-6) M), staurosporin (10(-8) M), or okadaic acid (10(-7) M) with an effective concentration. However, staurosporin had a partial inhibiting effect on the IGF-I or the IGF-I plus zinc-induced increases in cellular protein, although okadaic acid entirely blocked the IGF-I or the IGF-I plus zinc effect. The present study demonstrates that the anabolic effect of IGF-I in osteoblastic cells is enhanced by zinc ion. The enhancement by zinc may be mediated through the signaling pathway of protein kinase C and protein phosphatase in the cells.
在体外研究了骨形成激活剂锌是否调节胰岛素样生长因子-I（IGF-I）对成骨MC3T3-E1细胞的合成代谢作用。传代培养3天后，将细胞与IGF-I（10^(-8) M）一起培养72小时。该肽使细胞中的蛋白质浓度、脱氧核糖核酸（DNA）含量和细胞数量显著增加。硫酸锌（10^(-5) M）的存在显著增强了这些增加，但锌螯合二肽（β-丙氨酰-L-组氨酸锌；10^(-5) M）则没有这种作用。此外，IGF-I和硫酸锌同时存在时，细胞碱性磷酸酶活性协同增加。然而，胰岛素（10^(-8) M）和硫酸锌（10^(-5) M）同时存在时未观察到这种效应。硫酸锌增强IGF-I诱导的细胞碱性磷酸酶活性和蛋白质浓度的作用明显被有效浓度的放线菌酮（10^(-6) M）、星形孢菌素（10^(-8) M）或冈田酸（10^(-7) M）所抑制。然而，星形孢菌素对IGF-I或IGF-I加锌诱导的细胞蛋白质增加有部分抑制作用，而冈田酸则完全阻断了IGF-I或IGF-I加锌的作用。本研究表明，锌离子增强了IGF-I对成骨细胞的合成代谢作用。锌的增强作用可能是通过细胞中蛋白激酶C和蛋白磷酸酶的信号通路介导的。
