目的研究AMP激活的蛋白激酶(AMPK)特异性激动剂AICAR对心肌细胞FOXO1转录因子活性及泛素连接酶MuRF1蛋白表达的影响,探讨AMPK对心肌细胞蛋白质降解通路的可能作用。方法培养出生1~3d大鼠心肌细胞,用AICAR干预激活AMPK,并用Western blotting检测其对FOXO1转录因子活性,以及MuRF1蛋白表达的影响。结果 AICAR能够激活心肌细胞AMPK,与对照组比较,AMPK激活后显著抑制FOXO1磷酸化(P〈0.01),促进MuRF1蛋白表达(P〈0.01)。结论 AMPK可能通过激活心肌细胞FOXO1的转录活性,上调MuRF1蛋白表达,参与心肌细胞蛋白质降解的调控。
Objective To investigate the effects of AICAR on the activity of transcription factor FOXO1 and expression of ubiquitin ligase MuRF1 in rat cardiomyocytes,and explore the possible role of AMP-activated protein kinase(AMPK) in proteolysis pathways.Methods In vitro cultured neonatal rat cardiac myocytes were treated with AICAR,and Western blotting was used to detect the phosphorylation of FOXO1 and expression of MuRF1 in the cells.Results AICAR activated AMPK in rat cardiac myocytes.Activated AMPK significantly inhibited the phosphorylation of FOXO1 and increased MuRF1 protein expression.Conclusion AMPK may regulate proteolysis by activating FOXO1 transcription factor and up-regulating MuRF1 expression.