Parstatin, the Cleaved Peptide on Proteinase-Activated Receptor 1 Activation, Is a Potent Inhibitor of Angiogenesis
Parstatin, the Cleaved Peptide on Proteinase-Activated Receptor 1 Activation, Is a Potent Inhibitor of Angiogenesis
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Parstatin 是蛋白酶激活受体 1 激活过程中的裂解肽，是一种有效的血管生成抑制剂
DOI：
10.1124/jpet.108.145664
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发表时间：
2009
影响因子：
3.5
通讯作者：
N. Tsopanoglou
中科院分区：
文献类型：
--
作者：
Panagiota Zania;Despina Gourni;A. Aplin;R. Nicosia;C. Flordellis;M. Maragoudakis;N. Tsopanoglou
凝血酶对蛋白酶激活受体1的蛋白水解激活揭开了拴系的肽配体并切割41个氨基酸的肽。在这份报告中，我们表明，这种肽，我们已经指定为“parstatin”，是一种有效的血管生成抑制剂。合成parstatin抑制基本的血管生成和刺激的碱性成纤维细胞生长因子和血管内皮生长因子在鸡胚模型在体内和大鼠主动脉环测定。Parstatin还在体外废除了基质胶和纤维蛋白血管生成模型上的内皮细胞迁移和毛细血管样网络形成。用parstatin处理内皮细胞通过以特异性和可逆的方式抑制细胞外信号调节激酶的磷酸化，并通过涉及半胱天冬酶激活的机制促进细胞周期停滞和凋亡，从而抑制细胞生长。我们已经表明，parstatin作为一种细胞穿透肽，发挥其生物学效应的细胞内。细胞摄取和抑制活性依赖于parstatin的疏水区。这些结果支持的概念，parstatin可能代表一个重要的负调节血管生成与可能的治疗应用。
The proteolytic activation by thrombin of the proteinase-activated receptor 1 unveils the tethered peptide ligand and cleaves a 41-amino acid peptide. In this report, we show that this peptide, which we have designated as “parstatin,” is a potent inhibitor of angiogenesis. Synthesized parstatin suppressed both the basic angiogenesis and that stimulated by basic fibroblast growth factor and vascular endothelial growth factor in the chick embryo model in vivo and in the rat aortic ring assay. Parstatin also abrogated endothelial cell migration and capillary-like network formation on the Matrigel and fibrin angiogenesis models in vitro. Treatment of endothelial cells with parstatin resulted in inhibition of cell growth by inhibiting the phosphorylation of extracellular signal-regulated kinases in a specific and reversible fashion and by promoting cell cycle arrest and apoptosis through a mechanism involving activation of caspases. We have shown that parstatin acts as a cell-penetrating peptide, exerting its biological effects intracellularly. The uptake into cells and the inhibitory activity were dependent on parstatin hydrophobic region. These results support the notion that parstatin may represent an important negative regulator of angiogenesis with possible therapeutic applications.
影响因子：
11.2
作者：
M. Caunt;Liang Hu;T. Tang;P. Brooks;S. Ibrahim;S. Karpatkin
通讯作者：
M. Caunt;Liang Hu;T. Tang;P. Brooks;S. Ibrahim;S. Karpatkin