SIRT6 overexpression inhibits AngⅡ-induced cardiomyocyte apoptosis by activating AMPK/Nrf2/HO-1 pathway
10.20039/j.cnki.1007-3949.2024.08.003
- VernacularTitle:SIRT6过表达激活AMPK/Nrf2/HO-1通路抑制AngⅡ诱导的心肌细胞凋亡
- Author:
Zhenhua LU
1
;
Jing SHEN
;
Wenjun HUANG
;
Wei SUN
;
Yongxiang MA
Author Information
1. 南京医科大学附属江苏盛泽医院心血管内科,江苏省苏州市 215200
- Keywords:
recombinant sirtuin 6;
adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor/heme oxygenase-1;
oxidative stress;
DNA injury;
apoptosis
- From:
Chinese Journal of Arteriosclerosis
2024;32(8):663-668,676
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate whether SIRT6 overexpression inhibits angiotensin Ⅱ(Ang Ⅱ)-induced cardio-myocyte apoptosis by activating adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase-1(AMPK/Nrf2/HO-1)signaling pathway.Methods The experiment was divided into 4 groups:control group,AngⅡ group,Ang Ⅱ+SIRT6 group,Ang Ⅱ+empty vector(EV)group.The mRNA level of SIRT6 was detected by RT-PCR.The cell activity was measured by MTT assay.The cell apoptosis was analyzed by flow cy-tometry.SIRT6,cardiomyocyte apoptosis related proteins(Bax,cleaved Caspase-3,Bcl-2),DNA damage related pro-teins(γ-H2AX,p-ATM),AMPK/Nrf2/HO-1 signaling pathway related proteins(p-AMPK,Nrf2,HO-1)were measured by Western blot.The reactive oxygen species(ROS)content was determined by DCFH-DA staining.The changes of the above indexes among the groups were observed.Results Compared with control group,the mRNA and protein ex-pression levels of SIRT6 and cell activity were significantly decreased in Ang Ⅱ group.Apoptosis rate,the expressions of Bax,cleaved Caspase-3 were increased,and the expression of Bcl-2 was decreased.The expressions of γ-H2AX and p-ATM were increased,and the expressions of p-AMPK,Nrf2,HO-1 were decreased.The activity of ROS was increased(P＜0.01).Compared with Ang Ⅱ+EV group,the expression of SIRT6 and cell activity were significantly increased in Ang Ⅱ+SIRT6 group.Apoptosis rate,the expressions of Bax and cleaved Caspase-3 were decreased,and the expression of Bcl-2 was increased.The expressions of γ-H2AX and p-ATM were decreased,the expressions of p-AMPK,Nrf2,HO-1 were increased.The activity of ROS was decreased(P＜0.01).Conclusion SIRT6 overexpression inhibits Ang Ⅱ-induced cardiomyocyte apoptosis through activation of AMPK/Nrf2/HO-1 signaling pathway.
