Hanai Yoshiteru, Tokuda Haruhiko, Yasuda Eisuke, Noda Takahiro, Ohta Toshiki, Takai Shinji, Kozawa Osamu
Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Life Sci. 2006 Dec 23;80(3):230-4. doi: 10.1016/j.lfs.2006.09.003. Epub 2006 Sep 16.
We previously reported that basic fibroblast growth factor (FGF-2) activates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether zinc affects the VEGF release by FGF-2 in MC3T3-E1 cells. The FGF-2-induced VEGF release was significantly enhanced by ZnSO(4) but not Na(2)SO(4). The enhancing effect of ZnSO(4) was dose-dependent between 1 and 100 muM. ZnSO(4) markedly enhanced the FGF-2-induced phosphorylation of p44/p42 MAP kinase while having little effect on the SAPK/JNK phosphorylation. PD98059 significantly reduced the amplification by ZnSO(4) of the FGF-2-stimulated VEGF release. Taken together, our findings strongly suggest that zinc enhances FGF-2-stimulated VEGF release resulting from up-regulating activation of p44/p42 MAP kinase in osteoblasts.
我们先前报道过，碱性成纤维细胞生长因子（FGF-2）可激活应激激活蛋白激酶/c-Jun氨基末端激酶（SAPK/JNK）和p44/p42丝裂原活化蛋白（MAP）激酶，从而刺激成骨样MC3T3-E1细胞释放血管内皮生长因子（VEGF）。在本研究中，我们调查了锌是否会影响MC3T3-E1细胞中FGF-2诱导的VEGF释放。硫酸锌可显著增强FGF-2诱导的VEGF释放，但硫酸钠则无此作用。硫酸锌的增强作用在1至100μM之间呈剂量依赖性。硫酸锌显著增强了FGF-2诱导的p44/p42 MAP激酶的磷酸化，而对SAPK/JNK磷酸化影响很小。PD98059显著降低了硫酸锌对FGF-2刺激的VEGF释放的放大作用。综上所述，我们的研究结果强烈表明，锌通过上调成骨细胞中p44/p42 MAP激酶的激活来增强FGF-2刺激的VEGF释放。
