ABSTRACT

Resveratrol is a natural polyphenol with beneficial antioxidant properties. It suppresses the migration of osteoblast-like MC3T3-E1 cells induced by epidermal growth factor, via SIRT1-mediated inhibition of SAPK/JNK and Akt. Moreover, insulin-like growth factor-I (IGF-I) stimulates the migration involving the pathways of p44/p42 mitogen-activated protein (MAP) kinase and Akt. Therefore, we investigated the effects of resveratrol on IGF-I-induced cell migration. Resveratrol and SRT1720, an activator of SIRT1, suppressed IGF-I-induced migration. Inauhzin, a SIRT1 inhibitor, significantly rescued the inhibition of IGF-I-induced cell migration by resveratrol. Resveratrol inhibited IGF-I-induced phosphorylation of p44/p42 MAP kinase but not Akt. SRT1720 inhibited IGF-I-induced phosphorylation of p44/p42 MAP kinase. Furthermore, PD98059, p44/p42 MAP kinase inhibitor, alone suppressed IGF-I-induced osteoblast migration, but did not affect the suppressive effect of resveratrol when administered concomitantly. These findings strongly suggest that resveratrol suppresses IGF-I-induced osteoblast migration via SIRT1 activation at least partially by attenuating the p44/p42 MAP kinase pathway.

摘要

白藜芦醇是具有有益抗氧化性能的天然多酚。它通过SIRT1介导的SAPK / JNK和Akt抑制作用抑制表皮生长因子诱导的成骨样MC3T3-E1细胞的迁移。此外，胰岛素样生长因子-I（IGF-I）刺激涉及p44 / p42丝裂原活化蛋白（MAP）激酶和Akt途径的迁移。因此，我们调查了白藜芦醇对IGF-I诱导的细胞迁移的影响。白藜芦醇和SIRT1的激活剂SRT1720抑制了IGF-I诱导的迁移。SIRT1抑制剂Inauhzin大大缓解了白藜芦醇对IGF-I诱导的细胞迁移的抑制作用。白藜芦醇抑制IGF-I诱导的p44 / p42 MAP激酶的磷酸化，但不抑制Akt。SRT1720抑制了IGF-I诱导的p44 / p42 MAP激酶的磷酸化。此外，PD98059，单独使用p44 / p42 MAP激酶抑制剂可抑制IGF-I诱导的成骨细胞迁移，但同时给药时不会影响白藜芦醇的抑制作用。这些发现强烈表明白藜芦醇通过减弱p44 / p42 MAP激酶途径至少部分通过SIRT1激活抑制了IGF-I诱导的成骨细胞迁移。