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Effect of Endothelin on Sodium/Hydrogen Exchanger Activity of Human Monocytes and Atherosclerosis-Related Functions

机译:内皮素对人单核细胞钠/氢交换子活性及动脉粥样硬化相关功能的影响

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The objective of this article is to investigate the influence of endothelin-1 (ET-1) on human monocyte Na~+/H~+ exchanger (NHE) ac tivity and on the atherosclerosis-related monocyte functions. ET-1 caused an increase in pHi and in ~(22)Na influx of monocytes. A reversal of ET-1 effect on pHi was observed in the presence of the NHE1 inhibitor, cariporide. In addition, the activation of NHE1 by ET-1 was mediated via protein kinase C (PKC), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and NADPH oxidase. Also, a link between ET-1 and nitric oxide (NO) was observed. Furthermore, after ET-1 treatment, an increase of the adhesive capacity, the migration abil ity on laminin and CD36 expression of monocytes, was observed; using cariporide this increase was abolished. Our results showed that ET-1 in duces a signaling pathway with the involvement of PKC, MAPK, PI3K, and NADPH oxidase where NHE1 plays a key role. ET-1 also plays a sig nificant role in atherosclerosis-related functions of human monocytes, via NHE1 activation.
机译:本文的目的是研究内皮素-1(ET-1)对人单核细胞Na〜+ / H〜+交换子(NHE)活性以及与动脉粥样硬化相关的单核细胞功能的影响。 ET-1引起pHi和单核细胞〜(22)Na流入增加。在NHE1抑制剂cariporide存在下,观察到ET-1对pHi的作用逆转。此外,ET-1对NHE1的激活是通过蛋白激酶C(PKC),有丝分裂原激活的蛋白激酶(MAPK),磷脂酰肌醇3-激酶(PI3K)和NADPH氧化酶介导的。此外,观察到ET-1和一氧化氮(NO)之间的联系。此外,在ET-1处理后,观察到粘附能力的增加,层粘连蛋白的迁移能力和单核细胞CD36表达的增加。使用卡立泊来德,这种增加被取消了。我们的研究结果表明,ET-1通过PKC,MAPK,PI3K和NADPH氧化酶(其中NHE1起关键作用)的参与诱导了信号通路。 ET-1还通过NHE1激活在人类单核细胞的动脉粥样硬化相关功能中起着重要作用。

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