Activation of adenosine A2b receptor attenuates high glucose-induced apoptosis in H9C2 cells via PI3K/Akt signaling
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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.
KeywordsAdenosine A2b receptor H9C2 cells Apoptosis High glucose PI3K/Akt
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Conflict of interest
The authors declare that they have no conflict of interest.
- Grube K, Rudebusch J, Xu Z, Bockenholt T, Methner C, Muller T, Cuello F, Zimmermann K, Yang X, Felix SB, Cohen MV, Downey JM, Krieg T (2011) Evidence for an intracellular localization of the adenosine A2B receptor in rat cardiomyocytes. Basic Res Cardiol 106:385–396CrossRefPubMedPubMedCentralGoogle Scholar
- International Diabetes Federation (IDF) (2015) IDF diabetes atlas (7th edition. Available at http://www.diabetesatlas.org/. Accessed December 12, 2015). IDF diabetes atlas
- Pan Y, Wang Y, Zhao Y, Peng K, Li W, Wang Y, Zhang J, Zhou S, Liu Q, Li X, Cai L, Liang G (2014) Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucose-induced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy. Diabetes 63:3497–3511CrossRefPubMedGoogle Scholar
- Sun S, Yang S, Dai M, Jia X, Wang Q, Zhang Z, Mao Y (2017) The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose-stimulated H9C2 cells. BMC Complement Altern Med 17:310CrossRefPubMedPubMedCentralGoogle Scholar