PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells
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Cardiovascular disease is a growing major global public health problem. Oxidative stress is regarded as one of the key regulators of pathological physiology, which eventually leads to cardiovascular disease. However, mechanisms by which FGF-2 rescues cells from oxidative stress damage in cardiovascular disease is not fully elucidated. Herein this study was designed to investigate the protective effects of FGF-2 in H2O2-induced apoptosis of H9c2 cardiomyocytes, as well as the possible signaling pathway involved. Apoptosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using methyl thiazolyl tetrazolium assay, Hoechst, and TUNEL staining. Cells were pretreated with PI3K/Akt inhibitor LY294002 to investigate the possible PI3K/Akt pathways involved in the protection of FGF-2. The levels of p-Akt, p-FoxO3a, and Bim were detected by immunoblotting. Stimulation with H2O2 decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by PI3K/Akt inhibitor LY294002. In conclusion, our data suggest that FGF-2 protects against H2O2-induced apoptosis of H9c2 cardiomyocytes via activation of the PI3K/Akt/FoxO3a pathway.
KeywordsFGF-2 Forkhead transcription factor Apoptosis Cardiomyocytes Akt
This work was supported by grants from the National Natural Science Foundation of China (81470435, 81170277, ZS Jiang), Specialized Research Fund for the Doctoral Program of Higher Education, Ministry of Education of China (20124324110003,ZS Jiang), the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province (2008-244, ZS Jiang), Applied Basic Research Project of the Department of Science and Technology of Hunan Province(2014FJ6088, LJ Peng), Health Department of Hunan province 2011 annual scientific research project(B2011-041), Graduate student research innovation project of Hunan province (CX2013B397), and Hunan province college students inquiry learning and innovative experimental project in 2010 (No:475).
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