Department of Pharmacology, Gifu University Graduate School of Medicine , Gifu, Japan.
Department of Dermatology, Kizawa Memorial Hospital , Minokamo, Japan.
Biosci Biotechnol Biochem. 2020 Dec;84(12):2428-2439. doi: 10.1080/09168451.2020.1809987. Epub 2020 Aug 30.
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.
白藜芦醇是一种天然多酚，具有有益的抗氧化特性。它通过 SIRT1 介导的 SAPK/JNK 和 Akt 抑制，抑制表皮生长因子诱导的成骨样 MC3T3-E1 细胞迁移。此外，胰岛素样生长因子-I（IGF-I）刺激迁移涉及 p44/p42 丝裂原激活蛋白（MAP）激酶和 Akt 途径。因此，我们研究了白藜芦醇对 IGF-I 诱导的细胞迁移的影响。白藜芦醇和 SIRT1 激活剂 SRT1720 抑制 IGF-I 诱导的迁移。SIRT1 抑制剂 inauhzin 显著挽救了白藜芦醇对 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 激酶磷酸化，但不影响 Akt。SRT1720 抑制 IGF-I 诱导的 p44/p42 MAP 激酶磷酸化。此外，PD98059，p44/p42 MAP 激酶抑制剂，单独抑制 IGF-I 诱导的成骨细胞迁移，但不影响同时给予白藜芦醇时的抑制作用。这些发现强烈表明，白藜芦醇通过 SIRT1 激活抑制 IGF-I 诱导的成骨细胞迁移，至少部分通过减弱 p44/p42 MAP 激酶途径。
