miR-124 通过抑制 p66Shc 介导的氧化应激减轻阿霉素诱导的心脏损伤。
MiR-124 attenuates doxorubicin-induced cardiac injury via inhibiting p66Shc-mediated oxidative stress.
机构信息
Department of Cardiology, the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an 223001, China.
Nanjing Medical Univeristy, China.
出版信息
Biochem Biophys Res Commun. 2020 Jan 8;521(2):420-426. doi: 10.1016/j.bbrc.2019.10.157. Epub 2019 Oct 28.
Previous studies showed that miR-124 had a protective role by reducing oxidant stress and preventing cell apoptosis and autophagy. However, its role in doxorubicin-induced cardiomyopathy was less known. In our study, we confirmed increased ROS and decreased expression of miR-124 in doxorubicin-treated heart tissues and primary cardiomyocytes. The oxidative stress and cell apoptosis were alleviated by overexpressing miR-124, characterized by decreased activity of MDA and increased activity of SOD. While inhibiting miR-124 generated opposed effects. Mechanistically, our bioinformatic prediction and luciferase assay confirmed that miR-124 inhibited the expression of p66Shc, a proapoptotic signaling pathway. Our results suggested that miR-124 was hopeful to become a therapeutic target in doxorubicin-related cardiomyopathy.
先前的研究表明，miR-124 通过减少氧化应激、防止细胞凋亡和自噬发挥保护作用。然而，其在阿霉素诱导的心肌病中的作用知之甚少。在本研究中，我们证实了在阿霉素处理的心脏组织和原代心肌细胞中 ROS 增加和 miR-124 表达减少。过表达 miR-124 可减轻氧化应激和细胞凋亡，表现为 MDA 活性降低和 SOD 活性增加。而抑制 miR-124 则产生相反的效果。从机制上讲，我们的生物信息学预测和荧光素酶测定证实 miR-124 抑制了促凋亡信号通路 p66Shc 的表达。我们的结果表明，miR-124 有望成为阿霉素相关心肌病的治疗靶点。
Zotero 插件