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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells
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Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells

机译：姜黄素抑制A-10血管平滑肌细胞中胰岛素样生长因子-1诱导的PKB信号和Egr-1的表达

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摘要

Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the signaling pathways responsible for inducing hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). We have previously demonstrated that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and proliferative responses of angiotensin II (Ang-II) and endothelin-1 (ET-1). Curcumin, a polyphenolic compound derived from the spice turmeric is known to possess antiproliferative properties and exerts vasculoprotective effects. However, the ability of curcumin to modulate IGF-1-induced signaling responses in VSMC remains to be investigated. In this study, we determined the effect of curcumin on IGF-1-induced phosphorylation of protein kinase B (PKB), glycogen synthase kinase-3β (GSK-3β), and IGF-1R in VSMC. Curcumin inhibited IGF-1-induced phosphorylation of PKB and GSK-3β as well as the IGF-1R β subunit in a dose-dependent fashion. In addition, IGF-1-induced expression of early growth response protein 1 (Egr-1) which plays a pathogenic role in vascular dysfunctions, was also attenuated by curcumin. In conclusion, these results indicate that curcumin is a potent inhibitor of key components of the IGF-1-induced mitogenic and proliferative signaling system in VSMC, and suggest that curcumin-induced attenuation of these signaling components may constitute a potential mechanism for its vasculoprotective effects.
机译：胰岛素样生长因子1（IGF-1）是一种促有丝分裂因子，可刺激负责诱导血管平滑肌细胞（VSMC）肥大和增殖反应的信号通路。我们以前已经证明，IGF-1受体（IGF-1R）在转导血管紧张素II（Ang-II）和内皮素1（ET-1）的肥大和增殖反应中起关键作用。姜黄素是衍生自香料姜黄的多酚化合物，具有抗增殖性能，并具有血管保护作用。然而，姜黄素调节VSMC中IGF-1诱导的信号传导反应的能力仍有待研究。在这项研究中，我们确定姜黄素对VSMC中IGF-1诱导的蛋白激酶B（PKB），糖原合酶激酶-3β（GSK-3β）和IGF-1R磷酸化的影响。姜黄素以剂量依赖的方式抑制IGF-1诱导的PKB和GSK-3β以及IGF-1Rβ亚基的磷酸化。此外，姜黄素还减弱了IGF-1诱导的早期生长反应蛋白1（Egr-1）的表达，该蛋白在血管功能障碍中起着致病作用。总之，这些结果表明姜黄素是VSMC中IGF-1诱导的有丝分裂和增殖信号系统关键成分的有效抑制剂，并表明姜黄素诱导的这些信号成分的衰减可能构成其血管保护作用的潜在机制。 。

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