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首页> 外文期刊>Molecular and Cellular Biology >Cyclic AMP Potentiates Vascular Endothelial Cadherin-Mediated Cell-Cell Contact To Enhance Endothelial Barrier Function through an Epac-Rap1 Signaling Pathway
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Cyclic AMP Potentiates Vascular Endothelial Cadherin-Mediated Cell-Cell Contact To Enhance Endothelial Barrier Function through an Epac-Rap1 Signaling Pathway

机译：循环AMP增强血管内皮钙黏着蛋白介导的细胞间接触，以通过Epac-Rap1信号通路增强内皮屏障功能。

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Cyclic AMP (cAMP) is a well-known intracellular signaling molecule improving barrier function in vascular endothelial cells. Here, we delineate a novel cAMP-triggered signal that regulates the barrier function. We found that cAMP-elevating reagents, prostacyclin and forskolin, decreased cell permeability and enhanced vascular endothelial (VE) cadherin-dependent cell adhesion. Although the decreased permeability and the increased VE-cadherin-mediated adhesion by prostacyclin and forskolin were insensitive to a specific inhibitor for cAMP-dependent protein kinase, these effects were mimicked by 8-(4-chlorophenylthio)-2′-O-methyladenosine-3′, 5′-cyclic monophosphate, a specific activator for Epac, which is a novel cAMP-dependent guanine nucleotide exchange factor for Rap1. Thus, we investigated the effect of Rap1 on permeability and the VE-cadherin-mediated cell adhesion by expressing either constitutive active Rap1 or Rap1GAPII. Activation of Rap1 resulted in a decrease in permeability and enhancement of VE-cadherin-dependent cell adhesion, whereas inactivation of Rap1 had the counter effect. Furthermore, prostacyclin and forskolin induced cortical actin rearrangement in a Rap1-dependent manner. In conclusion, cAMP-Epac-Rap1 signaling promotes decreased cell permeability by enhancing VE-cadherin-mediated adhesion lined by the rearranged cortical actin.
机译：环AMP（cAMP）是一种众所周知的细胞内信号分子，可改善血管内皮细胞的屏障功能。在这里，我们描述了一种新型的cAMP触发信号，该信号调节了屏障功能。我们发现，cAMP升高试剂，前列环素和毛喉素能降低细胞通透性并增强血管内皮（VE）钙粘着蛋白依赖性细胞粘附。尽管前列环素和毛喉素对通透性的降低和VE-钙粘蛋白介导的粘附的增加对cAMP依赖性蛋白激酶的特异性抑制剂不敏感，但这些作用被8-（4-氯苯硫基）-2'- O所模仿-甲基腺苷-3'，5'-环一磷酸，是Epac的特异性活化剂，它是Rap1的新型cAMP依赖性鸟嘌呤核苷酸交换因子。因此，我们通过表达组成型活性Rap1或Rap1GAPII来研究Rap1对通透性和VE-钙黏着蛋白介导的细胞粘附的影响。 Rap1的激活导致通透性的降低和VE-钙黏着蛋白依赖性细胞粘附的增强，而Rap1的失活具有相反的作用。此外，前列环素和毛喉素以Rap1依赖性方式诱导皮质肌动蛋白重排。总之，cAMP-Epac-Rap1信号传导通过增强VE-钙粘蛋白介导的重排皮质肌动蛋白内衬的粘附而促进细胞通透性降低。

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