Atorvastatin protects swine bone marrow mesenchymal stem cells from apoptosis through AMPK but not PI3K/Akt pathway
10.3760/cma.j.issn.0253-3758.2011.11.013
- VernacularTitle:阿托伐他汀主要经AMP蛋白激酶而非PI3K/Akt信号通路抑制猪骨髓间充质干细胞凋亡
- Author:
Lei SONG
1
;
Yue-Jin YANG
;
Qiu-Ting DONG
;
Hai-Yan QIAN
;
Hui XU
;
Xian-Min MENG
;
Yue TANG
Author Information
1. 北京协和医学院中国医学科学院阜外心血管病医院
- Keywords:
Mesenchymal stem cells;
Apoptosis;
Atorvostatin
- From:
Chinese Journal of Cardiology
2011;39(11):1033-1038
- CountryChina
- Language:Chinese
-
Abstract:
Objective The effect of mesenchymal stem cells (MSCs) transplantation is poor because of the harsh environment post infarction.Our previous studies have proven that Statins could enhance the implanted bone marrow MSCs survival,but the exact mechanism remained to be clarified.We hypothesized that atorvastatin (Ator) could protect MSCs from hypoxia and serum-free (H/SF) induced apoptosis and investigated the potential mechanisms.Methods Chinese mini-swine′s bone marrow derived MSCs were cultured in vitro and exposed to hypoxia and H/SF,Ator of various concentrations (0.001 - 10μmol/L),AMPK inhibitor-compound C ( CC),PI3K inhibitor-LY294002 (LY),Ator + CC and Ator +LY.Cell apoptosis was assessed using Annexin V/Propidine Iodine kit by flow cytometry.Phosphorylation of AMPK,Akt,endothelial nitric oxide synthase (eNOS) level and phosphorylation were tested with Western blot.Real Time-PCR was performed to analyze the gene expression of AMPK,Akt and eNOS.Results MSCs apoptosis in Ator (0.01 - 10 μmol/L) treated H/SF groups was significantly reduced compared with H/SF group ( 1.94％ - 6.10％ vs.10.94％,P ＜ 0.01 or 0.05).Apoptosis was higher in Ator + CC group than in 1 μmol/L Ator group (4.94％ + 0.98％ vs.2.59％ ± 0.84％,P ＜ 0.01 ) and similar between Ator + LY and 1 μmol/L Ator group ( 2.02％ ± 0.45％ vs.2.59％ ± 0.84％,P ＞ 0.05 ).The gene expressions of AMPK,Akt and eNOS were significantly upregulated in atorvastatin treated groups.Meanwhile,phosphorylation of AMPK and eNOS increased in MSCs treated with atorvastatin (P ＜0.01 or0.05).Phosphorylation of eNOS significantly correlated with AMPK phosphorylation (r = 0.599,P =0.004),but not with Akt phosphorylation ( P = 0.263).Conclusions Atorvastatin can protect MSCs from H/SF induced apoptosis through AMPK pathway,which resulting in activation of eNOS.
