| 年 雪,王小丽,于东升,胡巧云,张 佳,唐传峰,刘培玉,盛 亮.小檗碱通过抑制Traf2-MEKK1-MEK-ERK通路改善TNF-α诱导的胰岛素抵抗[J].,2017,17(36):7001-7007 |
| 小檗碱通过抑制Traf2-MEKK1-MEK-ERK通路改善TNF-α诱导的胰岛素抵抗 |
| Berberine improves TNF-α-induced Insulin Resistance in HepG2 cells through inhibiting Traf2-MEKK1-MEK-ERK Pathway |
| 投稿时间：2017-09-18 修订日期：2017-10-19 |
| DOI：10.13241/j.cnki.pmb.2017.36.001 |
| 中文关键词: 小檗碱 胰岛素抵抗 肿瘤坏死因子-α 细胞外信号调节激酶1/2 |
| 英文关键词: Berberine Insulin resistance TNF-α ERK1/2 |
| 基金项目:国家自然科学基金项目（81400613）；江苏省自然科学基金项目（BK20140901） |
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| 中文摘要: |
| 摘要 目的：探讨小檗碱对肿瘤坏死因子-α(TNF-α)所致人肝癌细胞株HepG2胰岛素抵抗的缓解作用及分子机制。方法：采用10 ng/mL TNF-α诱导HepG2细胞产生胰岛素抵抗，同时以1 μmol/L小檗碱处理细胞，通过Western blotting检测胰岛素通路信号分子(IRS1、AKT)和TNF-α通路信号分子(Traf2、MEKK1、MEK1/2、ERK1/2)的蛋白表达。此外，通过过表达或抑制TNF-α通路的信号分子(MEK1、ERK2)进一步探讨小檗碱靶点。结果：TNF-α抑制HepG2细胞AKT(Thr308、Ser473位点)和IRS1(酪氨酸位点)的磷酸化(P<0.05)，促进IRS1(Ser307位点)和ERK1/2的磷酸化(P<0.05)，而这一作用能够被小檗碱所逆转(P<0.05)。同时，TNF-α对AKT活性的抑制作用能够被ERK1/2或MEK1/2的抑制剂拮抗(P<0.05)。此外，小檗碱并不能改善持续激活型ERK2(CA)或MEK1(CA)对胰岛素通路的抑制作用(P>0.05)，但是能阻碍Traf2与MEKK1的相互作用(P<0.05)。结论：小檗碱通过抑制Traf2-MEKK1-MEK-ERK通路改善TNF-α诱导的胰岛素抵抗。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect and molecular mechanism of berberine on TNF-α-induced insulin resistance in HepG2 cells. Methods: HepG2 cells were treated with TNF-α to induce insulin resistance. Meanwhile, HepG2 cells were treated with or without berberine (BBR). The changes of protein expressions of insulin signaling (IRS1 and AKT) and TNF-α signaling (Traf2, MEKK1, MEK1/2, ERK1/2) were detected by Western blotting. In addition, the key target of BBR was studied by overexpression or inhibition the molecules in TNF-α signaling pathway (MEK1/2, ERK1/2). Results: TNF-α significantly inhibited the phosphorylation of AKT (Thr308 and Ser473) and tyrosine phosphorylation of IRS1(P<0.05), increased the phosphorylation of IRS1 (Ser307) and ERK1/2 (P<0.05), which could be reversed by BBR (P<0.05). Meanwhile, the inhibition of AKT activity by TNF-α could by reversed by the antagonist of ERK2 and MEK1 (P<0.05). In addition, BBR didn't affect the inhibition of insulin signal by continuously activating ERK2 or MEK1 (P>0.05), whereas blocking the interaction of Traf2 and MEKK1 (P<0.05). Conclusion: BBR could improve TNF-α-induced insulin resistance via inhibiting Traf2-MEKK1-MEK-ERK pathway. |
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