中国病理生理杂志2017，Vol.33Issue(9)：1558-1563,6.DOI:10.3969/j.issn.1000-4718.2017.09.004
AngⅡ/AT1R通路通过激活人脐静脉内皮细胞PP2A导致eNOS Ser1177磷酸化水平下调
Ang Ⅱ/AT1R pathway activates PP2A to down-regulate p-eNOS (Ser1177) in human umbilical vein endothelial cells
摘要
Abstract
AIM:To investigate whether angiotensin Ⅱ (Ang Ⅱ)/angiotensin Ⅱ type 1 receptor (AT1 R)pathway down-regulates endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation level in human umbilical vein endothelial cells by activating protein phosphatase 2A (PP2A).METHODS:Human umbilical vein endothelial cells were randomly divided into normal control (control) group,Ang Ⅱ group,candesartan (CAN;specific AT1R blocker) group and CAN pretreatment + Ang Ⅱ group.The protein levels of total eNOS,p-eNOS (Ser1177),PP2Ac,IPP2A2 and p-PP2Ac (Tyr307) were determined by Western blot.The content of NO in the cell culture medium was detected by chemical colorimetry.RESULTS:Compared with control group,the level of p-eNOS (Ser1177) and the content of NO decreased (P ＜0.05).Compared with the same concentration of Ang Ⅱ group,CAN pretreatment increased the level of p-eNOS (Ser1177) and the content of NO (P ＜ 0.05),but the protein expression of eNOS showed no significant difference.Compared with control group,the levels of p-PP2Ac (Tyr307) and IPP2A2 decreased (P ＜ 0.05).Compared with the same concentration of Ang Ⅱ group,CAN pretreatment increased the levels of p-PP2Ac (Tyr307) and IPP2A2 (P ＜ 0.05),but the protein expression of PP2Ac showed no significant difference.CONCLUSION:Ang Ⅱ down-regulates the level of p-eNOS (Ser1177),and decreases the production of NO in human umbilical vein endothelial cells via AT1 R pathway.This effect may be related to the reduction of p-PP2Ac (Tyr307) and protein expression of IPP2A2,which results in the enhancement of PP2A2 activity.Pretreatment with AT1 R blocker CAN increases p-PP2Ac (Tyr307) level and IPP2A2 protein expression,thus reducing the PP2A activity,and ultimately restoring eNOS Ser1177 phosphorylation level and eNOS activity.关键词
血管紧张素Ⅱ/血管紧张素Ⅱ1型受体/蛋白磷酸酶2A/内皮型一氧化氮合酶/磷酸化Key words
Angiotensin Ⅱ/Angiotensin Ⅱ type 1 receptor/Protein phosphatase 2A/Endothelial nitric oxide synthase/Phosphorylation分类
医药卫生引用本文复制引用
王阿磊,丁菁,王凌霄,张倩,黄华,姜君财,陆德琴..AngⅡ/AT1R通路通过激活人脐静脉内皮细胞PP2A导致eNOS Ser1177磷酸化水平下调[J].中国病理生理杂志,2017,33(9):1558-1563,6.基金项目
国家自然科学基金资助项目(No.31460267) （No.31460267）
贵州省科学基金资助项目(黔科合LH字[2014]7088) （黔科合LH字[2014]7088）
