Heat shock protein 90α-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta
Heat shock protein 90α-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta
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DOI：
10.1161/01.res.0000124979.46214.e3
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发表时间：
2004-04-16
影响因子：
20.1
通讯作者：
Kazlauskas, A
中科院分区：
文献类型：
--
作者：
Lei, HT;Romeo, G;Kazlauskas, A
本文的目标是 (1) 鉴定其表达受糖尿病调节的细胞表面蛋白；(2) 评估它们对糖尿病并发症的影响。我们从高葡萄糖处理的内皮细胞 (EC) 的膜部分中纯化了热休克蛋白 90α (Hsp90α)，作为糖尿病特异性噬菌体的结合伴侣。进一步的研究表明，高葡萄糖会升高培养细胞中的细胞表面 Hsp90α，而糖尿病会增加主动脉管腔表面上的 Hsp90α 数量。我们还发现高血糖或糖尿病促进了Hsp90α与膜联蛋白II的结合，并增加了主动脉EC表面膜联蛋白II的表达。最后，高血糖或糖尿病会增加纤溶酶活性，而膜联蛋白 II 抗体可以部分逆转这种变化。这些发现揭示了 Hsp90α 和膜联蛋白 II 之间新的葡萄糖调节相互作用，并提出了膜联蛋白 II 表达增加（促进纤溶酶生成）与糖尿病状态相关的凝血异常有关的可能性。
The goals of this article were (1) to identify cell surface proteins whose expression was regulated by diabetes and (2) to assess their contribution to diabetic complications. We purified heat shock protein 90alpha (Hsp90alpha) from the membrane fraction of high glucose-treated endothelial cells (ECs) as a binding partner for a diabetes-specific phage. Further investigation revealed that high glucose elevated cell surface Hsp90alpha in cultured cells, and that diabetes increased the amount of Hsp90alpha on the luminal surface of the aorta. We also found that high glucose or diabetes promoted the association of Hsp90alpha with annexin II and increased the expression of annexin II on the surface of aortic ECs. Finally, plasmin activity was increased by high glucose or diabetes, and this change was partially reversed with an annexin II antibody. These findings reveal a novel glucose-regulated interaction between Hsp90alpha and annexin II, and raise the possibility that increased expression of annexin II, which promotes the generation of plasmin, is linked to clotting abnormalities associated with the diabetic state.