Activation of adenosine A2b receptor attenuates high glucose-induced apoptosis in H9C2 cells via PI3K/Akt signaling

  • Yi Shen
  • Gang Tang
  • Pan Gao
  • Bin Zhang
  • Hang Xiao
  • Liang-Yi Si


High glucose plays a vital role in apoptosis in H9C2 cells. However, the exact molecular mechanism remains unclear. In this study, we aimed to evaluate the cardio-protective role of A2b receptor in high glucose-induced cardiomyocyte apoptosis via PI3K/Akt pathway. Adenosine A2b receptor agonist (Bay506583), antagonist (MRS1754), and Akt inhibitor (LY294002) were applied respectively to H9C2 cells before exposed to high glucose for 12 h. Apoptosis of H9C2 cells was determined by TUNEL assay and the apoptosis rate by flow cytometry. The protein level of adenosine A2b receptor, p-Akt, total Akt, cleaved capase-3, cleaved capase-9, bax, and bcl-2 was measured by western blotting. The results demonstrated that apoptosis of H9C2 cardiomyocytes triggered by high-glucose treatment was time-dependent. The protein level of A2b receptor and activated Akt was both decreased in cardiomyocyte with high-glucose treatment. Moreover, we found that high glucose-induced apoptosis in H9C2 cells could be attenuated by administration of adenosine A2b receptor agonist Bay606583. This effect could be reversed by Akt inhibitor LY294002. In conclusion, activation of A2b receptor could prevent high glucose-induced apoptosis of H9C2 cells in vitro to a certain extent by activating PI3K/Akt signaling. In conclusion, these results suggested that activation of A2b receptor could be a novel therapeutic approach to high glucose-induced cardiomyocyte injury.


Adenosine A2b receptor H9C2 cells Apoptosis High glucose PI3K/Akt 


Funding information

This study was supported by the Natural Science Foundation of Chongqing (Grant numbers: cstc2014jcyjA10071), the Science Foundation of Southwest hospital (Grant numbers: SWH2016JCYB-57), and the National Science Foundation of China (NSFC) (Grant numbers: 81370446).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© The Society for In Vitro Biology 2018

Authors and Affiliations

  1. 1.Department of Geriatrics, Southwest HospitalThird Military Medical University (Army Medical University)ChongqingChina

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