MKP-1在17β-雌二醇抑制ET-1诱导的心肌肥大反应中的调控作用

摘要

Objective To determine the regulation by MKP-1 of ERK1/2 activity and protein expression in 17β-estradiol (E2) inhibiting cardiomyocyte hypertrophy induced by ET-1. Methods The cell surface area, protein synthesis rate and protein content of cardiac muscle cells of neonatal rat were assayed to reflect cardiomyocyte hypertrophic condition. Protein expression of phospho-ERKl/2 and MKP-1 were detected by Western blot. Results ① E2 inhibited cardiomyocyte hypertrophy induced by ET-1. ②ET-1 significantly stimulated ERK1/2 activity, which was prevented by pretreatment with E2. ③On the stimulation with ET-1, E2 strongly increased the expression of MKP-1. Conclusions E2 can significantly induce the expression of MKP-1, then lead to the restraint of ERK1/2 activity induced by ET-1,which underlies important effect of E2 on inhibiting cardiomyocyte hypertrophy.%目的 从丝裂原活化蛋白激酶磷酸酶-1(MKP-1)的角度研究ERK1/2信号通路在17β-雌二醇(E2)抑制内皮素-1(ET-1)诱导的心肌肥大反应中的作用及其调控机制.方法 利用培养的新生大鼠心肌细胞,以蛋白合成速率、蛋白含量及细胞表面积作为心肌肥大反应指标,以免疫印迹法分别测定磷酸化ERK1/2及MKP-1蛋白的表达.结果 ①E2明显抑制ET-1诱导的心肌肥大反应;②E2可抑制ET-1诱导的ERK1/2活性增加;③ET-1刺激条件下,E2可使心肌细胞MKP-1蛋白表达进一步增加.结论 E2可通过增加心肌细胞MKP-1蛋白表达,抑制ET-1诱导的心肌细胞ERK1/2活性增高,从而抑制ET-1诱导的心肌肥大反应.