Rapamycin protects cardiomyocytes against anoxia/reoxygenation injury by inducing autophagy through the PI3k/Akt pathway.
10.1007/s11596-015-1381-x
- Author:
Lu-qiao WANG
1
;
Xiao-shu CHENG
;
Cha-hua HUANG
;
Bo HUANG
;
Qian LIANG
Author Information
1. Jiangxi Key Laboratory of Molecular Medicine, Nanchang University, Nanchang, 330006, China, wlq8360@163.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Autophagy;
drug effects;
Base Sequence;
Cells, Cultured;
DNA Primers;
Myocytes, Cardiac;
drug effects;
Phosphatidylinositol 3-Kinases;
metabolism;
Proto-Oncogene Proteins c-akt;
metabolism;
Rats;
Real-Time Polymerase Chain Reaction;
Reperfusion Injury;
prevention & control;
Sirolimus;
pharmacology
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(1):10-15
- CountryChina
- Language:English
-
Abstract:
The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation (A/R) injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes (NRVM) as an in vitro model of ischemial/reperfusion (I/R) injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin (20, 50, 100, 150 μmol/L), and pretreated with 10 mmol/L 3-methyladenine (3MA) for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-II, LC3-I, Bim, caspase-3, p-PI3KI, PI3KI, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-II/LC3-I, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KI and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.
