Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Resveratrol is able to protect myocardial cells from ischemia/reperfusion-induced injury. However, the mechanism has yet to be fully elucidated. In the present study, it is reported that resveratrol has a critical role in the control of Ca2+ overload, which is the primary underlying cause of ischemia/reperfusion injury. Hypoxia/reoxygenation (H/R) treatment decreased the cell viability and increased the apoptosis of H9c2 cells, whereas the caspase-3 and intracellular Ca2+ levels were greatly elevated compared with the control group. Treatment of H9c2 cells with resveratrol (5, 15 and 30 mu M) reduced caspase-3 expression and cardiomyocyte apoptosis in a dose-dependent manner, and the intracellular Ca2+ overload was also significantly decreased. Furthermore, Frizzled-2 and Wnt5a belong to the non-canonical Wnt/Ca2+ pathway, which have been demonstrated to be responsible for Ca2+ overload, and were thus detected in the present study. The results indicated that both the mRNA and protein expression levels of Frizzled-2 and Wnt5a in H/R-induced H9c2 cells were markedly increased compared with the levels found in normal cells, and treatment with resveratrol (5, 15 and 30 mu M) significantly reduced the expression of Frizzled-2 and Wnt5a compared with the H/R group. The results indicated that resveratrol protected myocardial cells from H/R injury by inhibiting the Ca2+ overload through suppression of the Wnt5a/Frizzled-2 pathway.