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PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells

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Abstract

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.

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Acknowledgments

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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    Authors and Affiliations

    1. Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan Province, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People’s Republic of China

      Mi-Hua Liu, Guo-Hua Li, Li-Jun Peng, Shun-Lin Qu, Juan Peng, Xin-Yuan Luo, Zhong Ren, Hui Tang, Lu-Shan Liu, Zhi-Han Tang & Zhi-Sheng Jiang

    2. Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

      Mi-Hua Liu

    3. Department of Science and Education, The Pediatric Academy of University of South China, Changsha, Hunan, 410007, People’s Republic of China

      Li-Jun Peng

    4. Department of Pathology, Affiliated Mawangdui Hospital, University of South China, Changsha, Hunan, 410016, People’s Republic of China

      Yuan Zhang

    5. Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

      Heng-Jing Hu

    6. Chuanshan College, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

      Yao Liu

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    1. Mi-Hua Liu
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    Correspondence to Zhi-Han Tang or Zhi-Sheng Jiang.

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    Mi-Hua Liu, Guo-Hua Li, and Li-Jun Peng have contributed equally to this work.

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    Liu, MH., Li, GH., Peng, LJ. et al. PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells. Mol Cell Biochem 414, 57–66 (2016). https://doi.org/10.1007/s11010-016-2658-5

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