Summary
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.
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This project was supported by grants from Natural National Science Foundation of China (No. 81260023), National Science and Technology Infrastructure Program (No. 2013BAI05B10), Graduate Innovation Special Fund of Jiangxi Province (No. YC2012-S029), and Graduate Innovation Special Fund of Jiangxi Province (No. YC2014-B019).
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Wang, Lq., Cheng, Xs., Huang, Ch. et al. Rapamycin protects cardiomyocytes against anoxia/reoxygenation injury by inducing autophagy through the PI3k/Akt pathway. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 10–15 (2015). https://doi.org/10.1007/s11596-015-1381-x
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DOI: https://doi.org/10.1007/s11596-015-1381-x