Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway
Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway
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DOI：
10.1016/j.bbrc.2008.11.110
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发表时间：
2009-01-16
影响因子：
3.1
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Chen, Chun-Juan;Yu, Wei;Wang, Wei
细胞凋亡导致的心肌细胞损失已被认为是心室重塑和心力衰竭的原因。据报道，缺血和缺氧诱导的心肌细胞凋亡在许多心脏病理学中发挥着重要作用。我们研究了白藜芦醇（Res）是否对心肌细胞缺血/缺氧具有直接的细胞保护作用。通过 TUNEL 和流式细胞术评估，将 H9c2 胚胎大鼠心脏来源的细胞暴露于缺氧 24 小时，导致细胞凋亡显着增加，而用 20 μM Res 处理大大减少了这些细胞中缺氧诱导的细胞凋亡。将细胞暴露于Res (20 μM)会导致SIRT1快速激活，这对FoxO1功能具有双重影响：SIRT1增加FoxO1诱导细胞周期停滞的能力，但抑制FoxO1诱导细胞死亡的能力。这种效应可以通过抑制 SIRT1 来逆转。我们的研究结果表明，Res 通过 SIRT1-FoxO1 通路抑制 H9c2 细胞中缺氧诱导的细胞凋亡。这种多酚可能具有预防心血管疾病的潜力，尤其是冠状动脉疾病（CAD）患者。 Crown 版权所有 (C) 2008 由 Elsevier Inc. 出版。保留所有权利
Loss of cardiomyocytes through apoptosis has been proposed as a cause of ventricular remodeling and heart failure. Ischemia- and hypoxia-induced apoptosis of cardiomyocytes reportedly plays an important role in many cardiac pathologies. We investigated whether resveratrol (Res) has direct cytoprotective effects against ischemia/hypoxia for cardiomyocytes. Exposure of H9c2 embryonic rat heart-derived cells to hypoxia for 24 h caused a significant increase in apoptosis, as evaluated by TUNEL and flow cytometry, while treatment with 20 mu M Res greatly decreased hypoxia-induced apoptosis in these cells. Exposure of the cells to Res (20 mu M) caused rapid activation of SIRT1, which had a dual effect on FoxO1 function: SIRT1 increased FoxO1's ability to induce cell cycle arrest, but inhibited FoxO1's ability to induce cell death. This effect could be reversed by SIRT1 inhibition. Results of our study indicate that Res inhibits hypoxia-induced apoptosis via the SIRT1-FoxO1 pathway in H9c2 cells. This polyphenol may have potential in preventing cardiovascular disease, especially in coronary artery disease (CAD) patients. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved