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首页> 外文期刊>Endothelium: Journal of endothelial cell research >Regulation of endothelial barrier function by the cAMP-dependent protein kinase.
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Regulation of endothelial barrier function by the cAMP-dependent protein kinase.

机译：cAMP依赖性蛋白激酶对内皮屏障功能的调节。

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Elevation of cAMP promotes the endothelial cell (EC) barrier and protects the lung from edema development. Thus, we tested the hypothesis that both increases and decreases in PKA modulate EC function and coordinate distribution of regulatory, adherence, and cytoskeletal proteins. Inhibition of PKA activity by RpcAMPS and activation by cholera toxin was verified by assay of kemptide phosphorylation in digitonin permeabilized EC. Inhibition of PKA by RpcAMPS or overexpression of the endogenous inhibitor, PKI, decreased monolayer electrical impedance and exacerbated the decreases produced by agonists (thrombin and PMA). RpcAMPS directly increased F-actin content and organization into stress fibers, increased co-staining of actin with both phosphatase 2B and myosin light chain kinase (MLCK), caused reorganization of focal adhesions, and decreased catenin at cell borders. These findings are similar to those evoked by thrombin. In contrast, cholera toxin prevented the agonist-induced resistance decrease and protein redistribution. Although PKA activation attenuated thrombin-induced myosin light chain (MLC) phosphorylation, PKA inhibition per se did not cause MLC phosphorylation or affect [Ca2+]i. These studies indicate that a decrease in PKA activity alone can produce disruption of barrier function via mechanisms not involving MLCK and support a central role for cAMP/PKA in regulation of cytoskeletal and adhesive protein function in EC which correlates with altered barrier function.
机译：cAMP的升高会促进内皮细胞（EC）屏障，并保护肺免受水肿的发展。因此，我们测试了PKA增加和减少均调节EC功能并协调调节，粘附和细胞骨架蛋白分布的假说。 RpcAMPS对PKA活性的抑制作用和霍乱毒素的激活作用通过在洋地黄素透化的EC中的肯普特磷酸化试验来验证。 RpcAMPS对PKA的抑制或内源性抑制剂PKI的过度表达，降低了单层电阻抗，并加剧了激动剂（凝血酶和PMA）产生的降低。 RpcAMPS直接增加F-肌动蛋白的含量和组织成应力纤维，增加肌动蛋白与磷酸酶2B和肌球蛋白轻链激酶（MLCK）的共染色，引起粘着斑的重组，并减少细胞边界处的连环蛋白。这些发现与凝血酶引起的发现相似。相反，霍乱毒素阻止了激动剂诱导的耐药性降低和蛋白质重新分布。尽管PKA激活减弱了凝血酶诱导的肌球蛋白轻链（MLC）的磷酸化，但PKA抑制本身并不引起MLC磷酸化或影响[Ca2 +] i。这些研究表明，单独的PKA活性降低可通过不涉及MLCK的机制破坏屏障功能，并支持cAMP / PKA在调节EC中与改变的屏障功能相关的细胞骨架和粘附蛋白功能中的核心作用。

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