PI3K/GSK-3β signaling pathway mediates cardiotrophin-1 cardioprotection against cardiocyte hypoxia-reoxygenation injury
10.3760/cma.j.issn.1671-0282.2009.08.011
- VernacularTitle:糖原合成酶激酶-3β介导心肌营养素-1对心肌细胞急性缺氧复氧损伤的作用
- Author:
Juxiang LI
;
Lei WAN
;
Hao DING
;
Zirong XIA
;
Hai SU
;
Sujuan YAN
;
Yanqing WU
;
Qinghua WU
;
Xiaoshu CHENG
- Publication Type:Journal Article
- Keywords:
Cardiomyocyte;
Injury;
Cardiotrophin- 1;
Phosphoinsitol 3' kinase/glycogen synthase kinase-3β;
Signal pathway
- From:
Chinese Journal of Emergency Medicine
2009;18(8):814-818
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of Cardiotrophin-1 (CT-1) on cardiocyte hypoxia-reoxygenation injury,and to investigate the signaling pathways involved in the protective effect. Method This study was carried out in Key Lab of Molecular Medicine in Jiangxi Province. Cardiomyocytes from the hearts of 2-day-old Sprague-Dawley neonatal rats were prepared by a modified method. Five groups were included in the study. Group (ⅰ): control, Group (ⅱ): hypoxia/reoxygeuation, Group (ⅲ): hypoxia / reoxygenation + CT-1, Group (iv) : CT- 1 + hypoxia/ reoxygenation + LY294002 (PIK3/Akt inhibitor), Group (ⅴ): CT-1 + hypoxia / reoxygenation +DMSO. The concentration of CT-1 was 10 ng/mL. Myocytes survival rote was evaluated by MTS method, apopto-sis, mitochondrial permeability transition pore (△ψm) and reactive oxygen species(ROS) were detected by flow cy-tometer, phosphorylased GSK-3β and PI3K protein by western blotting. Analysis of variance and q test as statistical methods was used to analyze the data. Results Cardiomyocyte apoptosis and ROS increased markedly after hy-poxia/reoxygenation,but cardiomyocyte survival rate and the level of △ψm [(40.55±4.25) vs. (86.28±7.15), P < 0.01]decreased significantly. With CT-1 intervention, cardiomyocyte survival rate increased markedly (87%),apoptosis and ROS reduced significantly. The level of △ψm increased, the level of phosphorylased GSK-3β and phosphorylased PI3K protein obviously increased. The effect of CT-1 was inhibited by LY294002, but no significant effect was observed on ceils survival in DMSO group, which confirmed that LY294002 specifically in-volved blocking the protective effect of CT-1. Conclusions CT-1 can protect cardiac cells against hypoxia- reoxy-genation injury, these effects are dependent upon its ability to activate the PI3K/GSK-3β pathway.
