Molecular and Cellular Biochemistry

, Volume 414, Issue 1–2, pp 57–66 | Cite as

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

  • Mi-Hua Liu
  • Guo-Hua Li
  • Li-Jun Peng
  • Shun-Lin Qu
  • Yuan Zhang
  • Juan Peng
  • Xin-Yuan Luo
  • Heng-Jing Hu
  • Zhong Ren
  • Yao Liu
  • Hui Tang
  • Lu-Shan Liu
  • Zhi-Han TangEmail author
  • Zhi-Sheng JiangEmail author


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.


FGF-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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mi-Hua Liu
    • 1
    • 2
  • Guo-Hua Li
    • 1
  • Li-Jun Peng
    • 1
    • 3
  • Shun-Lin Qu
    • 1
  • Yuan Zhang
    • 4
  • Juan Peng
    • 1
  • Xin-Yuan Luo
    • 1
  • Heng-Jing Hu
    • 5
  • Zhong Ren
    • 1
  • Yao Liu
    • 6
  • Hui Tang
    • 1
  • Lu-Shan Liu
    • 1
  • Zhi-Han Tang
    • 1
    Email author
  • Zhi-Sheng Jiang
    • 1
    Email author
  1. 1.Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan ProvinceUniversity of South ChinaHengyangPeople’s Republic of China
  2. 2.Department of Clinical Laboratory, Affiliated Nanhua HospitalUniversity of South ChinaHengyangPeople’s Republic of China
  3. 3.Department of Science and EducationThe Pediatric Academy of University of South ChinaChangshaPeople’s Republic of China
  4. 4.Department of Pathology, Affiliated Mawangdui HospitalUniversity of South ChinaChangshaPeople’s Republic of China
  5. 5.Department of Cardiology/Cardiac Catheterisation Lab, Second Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  6. 6.Chuanshan CollegeUniversity of South ChinaHengyangPeople’s Republic of China

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