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他汀类药物和三磷酸腺苷通过上皮细胞中的P2X7嘌呤能受体调节细胞核内的磷酸化蛋白激酶B。

Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells.

作者信息

Mistafa Oras, Högberg Johan, Stenius Ulla

机构信息

Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.

出版信息

Biochem Biophys Res Commun. 2008 Jan 4;365(1):131-6. doi: 10.1016/j.bbrc.2007.10.148. Epub 2007 Oct 31.

Abstract

Many studies have documented P2X7 receptor functions in cells of mesenchymal origin. P2X7 is also expressed in epithelial cells and its role in these cells remains largely unknown. Our data indicate that P2X7 regulate nuclear pAkt in epithelial cells. We show that low concentration of atorvastatin, a drug inhibiting HMG-CoA reductase and cholesterol metabolism, or the natural agonist extracellular ATP rapidly decreased the level of insulin-induced phosphorylated Akt in the nucleus. This effect was seen within minutes and was inhibited by P2X7 inhibitors. Experiments employing P2X7 siRNA and HEK293 cells heterologously expressing P2X7 and in vivo experiments further supported an involvement of P2X7. These data indicate that extracellular ATP and statins via the P2X7 receptor modulate insulin-induced Akt signaling in epithelial cells.

摘要

许多研究记录了P2X7受体在间充质来源细胞中的功能。P2X7也在上皮细胞中表达,其在这些细胞中的作用在很大程度上仍不清楚。我们的数据表明,P2X7调节上皮细胞中的核pAkt。我们发现,低浓度的阿托伐他汀(一种抑制HMG-CoA还原酶和胆固醇代谢的药物)或天然激动剂细胞外ATP能迅速降低胰岛素诱导的细胞核中磷酸化Akt的水平。这种效应在几分钟内即可观察到,并被P2X7抑制剂所抑制。使用P2X7 siRNA的实验以及异源表达P2X7的HEK293细胞和体内实验进一步支持了P2X7的参与。这些数据表明,细胞外ATP和他汀类药物通过P2X7受体调节上皮细胞中胰岛素诱导的Akt信号传导。

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