[Angiotensin Ⅱ inhibits AMPK/SIRT1 pathway by inducing oxidative stress in RAW264.7 macrophages].

作者：Xiao S; Ma Y; Li J; Zhang Y; He H; Fang C; Wang W

来源：Journal of Southern Medical University, 2021, 41(3): 384-390.

DOI：10.12122/J.ISSN.1673-4254.2021.03.10

• AMPK/SIRT1
• RAW264.7 macrophages
• angiotensin Ⅱ
• oxidative stress

To investigate the mechanism by which angiotensin Ⅱ-induced oxidative stress response inhibits AMPK/ SIRT1 signaling in RAW264.7 macrophages.;RAW264.7 cells were treated with 0.5, 1, 3, 10, or 20 μmol/L angiotensin Ⅱ for 24 h, and the changes in the expressions of AMPK, p-AMPK, and SIRT1 proteins were detected using Western blotting. The intracellular ROS release level was measured and the levels of SOD and MDA were detected. The effects of angiotensin Ⅱ type 1 receptor (AT1R) gene silencing on the cell response to angiotensin Ⅱ treatment were examined by detecting the changes in AMPK, p-AMPK and SIRT1 protein levels. The effects of a ROS inhibitor on cellular AMPK and SIRT1 were also examined.;Angiotensin Ⅱ stimulation at 20 μmol/L significantly inhibited the phosphorylation of AMPK protein and increased cellular ROS release (P \u003c 0.05). Treatment with 0.5-10 μmol/L angiotensin Ⅱ did not cause significant changes in SOD activity or MDA expression, but angiotensin Ⅱ at the dose of 20 μmol/L significantly inhibited SOD activity in the cells (P \u003c 0.05). In the macrophages with AT1R gene silencing, treatment with angiotensin Ⅱ did not obviously inhibit AMPK phosphorylation or down- regulate SIRT1 expression. In cells treated with the ROS inhibitor, angiotensin Ⅱ failed to lower the level of AMPK phosphorylation or the expression of SIRT1.;Angiotensin Ⅱ induces oxidative stress to cause disturbance of AMPK/ SIRT1 signaling pathway in macrophages.

• 单位
  华中科技大学; 广州中医药大学