Resveratrol attenuates hypoxia/reoxygenation‑induced Ca2+ overload by inhibiting the Wnt5a/Frizzled‑2 pathway in rat H9c2 cells.
Resveratrol attenuates hypoxia/reoxygenation‑induced Ca2+ overload by inhibiting the Wnt5a/Frizzled‑2 pathway in rat H9c2 cells.
复制标题
DOI：
10.3892/mmr.2014.2488
复制
发表时间：
2014-11
影响因子：
3.4
通讯作者：
Xiang Wu;Shan-shan Zhou;N. Zhu;Xianbao Wang;W. Jin;Xudong Song;Aihua Chen
中科院分区：
文献类型：
--
作者：
Xiang Wu;Shan-shan Zhou;N. Zhu;Xianbao Wang;W. Jin;Xudong Song;Aihua Chen
白藜芦醇能够保护心肌细胞免受缺血/再灌注引起的损伤。然而，其机制尚未完全阐明。在本研究中，据报道白藜芦醇在Ca2+超载的控制中具有关键作用，Ca2+超载是缺血/再灌注损伤的主要潜在原因。缺氧/再氧化（H/R）处理降低了细胞活力，增加了H9c2细胞的凋亡，而与对照组相比，caspase‑3和细胞内Ca2+水平显著升高。用白藜芦醇（5、15和30µM）处理H9c2细胞，以剂量依赖的方式降低caspase - 3表达和心肌细胞凋亡，细胞内Ca2+超载也显著降低。此外，frizzed‑2和Wnt5a属于非典型的Wnt/Ca2+通路，已被证明是Ca2+过载的原因，因此在本研究中被检测到。结果表明，与正常细胞相比，H/R诱导的H9c2细胞中Frizzled - 2和Wnt5a的mRNA和蛋白表达水平均显著升高，白藜芦醇（5、15和30µM）处理与H/R组相比，显著降低了Frizzled - 2和Wnt5a的表达。结果表明，白藜芦醇通过抑制Wnt5a/Frizzled‑2通路抑制Ca2+超载，从而保护心肌细胞免受H/R损伤。
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 µM) 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 µM) 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.