Pentamethylquercetin protects against cardiac remodeling via activation of Sestrin2
Pentamethylquercetin protects against cardiac remodeling via activation of Sestrin2
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DOI：
10.1016/j.bbrc.2019.03.031
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发表时间：
2019-04-30
影响因子：
3.1
通讯作者：
Liu, Hui
中科院分区：
文献类型：
--
作者：
Du, Jing-Xia;Wu, Jian-Zhao;Liu, Hui
氧化应激广泛参与心脏重构的病理生理过程。与抗氧化功能相关的分子可能是逆转心脏重构的理想靶点。Sestrin2是内源性抗氧化防御的重要组成部分，但对其在心脏重构中的病理生理作用知之甚少。本研究的目的是探讨Sestrin2是否与心脏重塑密切相关，以及五甲基栎素(PMQ)对心脏重塑的保护作用是否与Sestrin2内源性抗氧化系统上调有关。我们建立了横动脉缩窄(TAC)诱导的压力超负荷心肌重塑模型和异丙肾上腺素(ISO)诱导的新生大鼠心肌细胞(NRCM)肥大模型。结果显示，模型组大鼠心肌组织和NRCM中Sestrin2表达明显下调，Nrf2和HO-1表达降低，Keap1表达上调。PMQ明显改善心脏重构，纠正Sestrin2/Nrf2/Keap1的异常表达。Sestrin2小干扰RNA(SiRNA)可减弱PMQ对NRCM的保护作用，并取消其对Nrf2/Keap1通路的调节作用。综上所述，Sestrin2可能是PMQ抗心肌重构的重要靶点。(C)2019 Elsevier Inc.保留所有权利。
Oxidative stress is widely involved in pathophysiological processes of cardiac remodeling. Molecules associated with antioxidant functions may be ideal targets for reversing cardiac remodeling. Sestrin2 is the important component of endogenous antioxidant defense, while there is little information on the pathophysiological roles of it in cardiac remodeling. The aim of this study was to investigate whether Sestrin2 is closely involved in cardiac remodeling, and whether the protective effect of pentamethylquercetin (PMQ) on cardiac remodeling is related to upregulation of the Sestrin2 endogenous antioxidant system. We generated a transverse aorta constriction (TAC)-induced pressure-overload cardiac-remodeling model in mice, and also established an isoproterenol (ISO)-induced neonatal rat cardiomyocyte (NRCM) hypertrophy model. The data showed Sestrin2 expression was downregulated significantly, and Nrf2 and HO-1 expression was also reduced in myocardial tissue or NRCM of model group, whereas keap1 expression was upregulated. PMQ significantly ameliorated cardiac remodeling and rectified the abnormal expression of Sestrin2/Nrf2/keap1. Sestrin2 small interfering RNA (SiRNA) reduced the protective effect of PMQ on NRCMs, as well as abolished its regulating effect on the Nrf2/keap1 pathway. In conclusion, Sestrin2 may be an important target in the anti-myocardial remodeling of PMQ. (C) 2019 Elsevier Inc. All rights reserved.