Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes
Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes
复制标题
紫檀芪恢复 Sirt1 功能可减轻心肌细胞缺氧-复氧损伤。
DOI：
10.1016/j.ejphar.2016.02.052
复制
发表时间：
2016-04-05
影响因子：
5
通讯作者：
Zhang, Zheng
中科院分区：
文献类型：
--
作者：
Guo, Yan;Zhang, Li;Zhang, Zheng
缺血心肌的血液供应恢复导致心肌细胞损伤，这一过程称为缺血-再灌注损伤。过量的活性氧和细胞内钙离子导致细胞损伤，但sirt 1（一种多功能蛋白脱乙酰酶）参与再灌注诱导的细胞损伤仍不清楚。在此，我们发现，缺氧-复氧，缺血-再灌注损伤的体外模型，诱导H9 c2心肌细胞凋亡所揭示的半胱氨酸蛋白酶-3检测，Hoechst 33258染色，流式细胞仪分析和JC-1染色。分子对接分析表明，紫檀芪，白藜芦醇的天然二甲醚衍生物，结合sirt 1的酶活性口袋。重要的是，以0.1-3.0 μ M的低浓度应用紫檀芪使H9 c2细胞免于凋亡，其效果与20 μ M的白藜芦醇相当。从机制上讲，紫檀芪通过1）刺激sirt 1活性发挥其心脏保护作用，因为用sirt 1拮抗剂splitomicin预处理H9 c2细胞消除了紫檀芪的作用，2）增强sirt 1表达。因此，本研究表明，在缺血-再灌注过程中激活sitr 1具有心脏保护作用，并且天然化合物紫檀芪可用于治疗以减轻缺血-再灌注损伤。(C)2016爱思唯尔B. V.保留所有权利。
Restoration of blood supply to ischemic myocardium causes cardiomyocyte damage, a process known as ischemia-reperfusion injury. Excess reactive oxygen species and intracellular calcium contribute to cell damage but the involvement of sirt1, a versatile protein deacetylase in reperfusion-induced cell damage remains unknown. Here, we found that hypoxia-reoxygenation, an in vitro model of ischemia-reperfusion injury, induced H9c2 cardiomyocyte apoptosis as revealed by caspase-3 assay, Hoechst 33258 staining, flow cytometric analysis and JC-1 staining. Molecular docking analysis showed that, pterostilbene, a natural dimethyl ether derivative of resveratrol, binds to the enzymatic active pocket of sirt1. Importantly, application of pterostilbene at low concentrations of 0.1-3.0 mu M rescued H9c2 cells from apoptosis, an effect comparable with resveratrol at 20 mu M. Mechanistically, pterostilbene exerted its cardioprotective effects via 1) stimulation of sirt1 activity, since pretreatment of H9c2 cells with splitomicin, an antagonist of sirt1, removed the effects of pterostilbene, and 2) enhancement of sirt1 expression. Therefore, the present study demonstrates that activation of sitr1 during ischemia-reperfusion is cardioprotective and that the natural compound-pterostilbene-could be used therapeutically to alleviate ischemia-reperfusion injury. (C) 2016 Elsevier B.V. All rights reserved.