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首页> 外文期刊>Signal transduction: Receptors, mediators and genes: Official journal of the Signal Transduction Society >Angiotensin II effect on calcium mobilization and mitogen-activated protein kinase activation in human umbilical vein endothelial cells
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Angiotensin II effect on calcium mobilization and mitogen-activated protein kinase activation in human umbilical vein endothelial cells

机译:血管紧张素II对人脐静脉内皮细胞中钙动员和丝裂原激活的蛋白激酶活化的影响

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摘要

Angiotensin II (Ang II) stimulation of human umbilical vein endothelial cells (HUVEC) provoked a transient increase in intracellular calcium concentration ([Ca~(2+)]_i) and induced a phosphorylation on mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK). Treatment of HUVEC with Ca~(2+)-ATPase inhibitor thapsigargin or Ca~(2+) ionophore A23187 resulted in a significant increase in ERK1/2 phosphorylation. Ang II-stimulated ERK1/2 phosphorylation was sensitive to the pretreatment of cells with U73122, a selective phospholipase C (PLC) inhibitor, resulting in a pronounced decrease of ERK1/2 phosphorylation. Additionally, Ang II-induced ERK1/2 phosphorylation was prominently reduced by the removal of Ca~(2+) from extracellular medium. Furthermore, activation of ERK1/2 was mimicked by phorbol 12-myristate acetate, a protein kinase C (PKC) activator, while the Ang II-provoked ERK1/2 phosphorylation was markedly attenuated by a PKC inhibition after the treatment of HUVEC with GFX109203X, a specific PKC inhibitor. This study demonstrated that Ang II mediates an increase in the MAPK/ERK phosphorylation in HUVEC which is dependent on [Ca~(2+)]_i and PKC activation.
机译:血管紧张素II(Ang II)对人脐静脉内皮细胞(HUVEC)的刺激引起细胞内钙浓度([Ca〜(2 +)] _ i)的短暂升高,并诱导促分裂原激活的蛋白激酶/细胞外信号调节激酶磷酸化(MAPK / ERK)。用Ca〜(2 +)-ATPase抑制剂thapsigargin或Ca〜(2+)离子载体A23187处理HUVEC导致ERK1 / 2磷酸化显着增加。 Ang II刺激的ERK1 / 2磷酸化对用U73122(一种选择性磷脂酶C(PLC)抑制剂)预处理的细胞很敏感,导致ERK1 / 2磷酸化的明显降低。此外,通过从细胞外培养基中去除Ca〜(2 +),Ang II诱导的ERK1 / 2磷酸化显着降低。此外,ERK1 / 2的激活被佛波醇12-肉豆蔻酸酯乙酸酯(一种蛋白激酶C(PKC)激活剂)模拟,而Ang II诱导的ERK1 / 2磷酸化在用GFX109203X处理HUVEC后被PKC抑制显着减弱,特定的PKC抑制剂。这项研究表明,Ang II介导了HUVEC中MAPK / ERK磷酸化的增加,这取决于[Ca〜(2 +)] _ i和PKC的激活。

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