miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury.
miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury.
复制标题
DOI：
10.3390/ijms23031036
复制
发表时间：
2022-01-18
影响因子：
5.6
通讯作者：
Bonet F
中科院分区：
文献类型：
--
作者：
Toro R;Pérez-Serra A;Mangas A;Campuzano O;Sarquella-Brugada G;Quezada-Feijoo M;Ramos M;Alcalá M;Carrera E;García-Padilla C;Franco D;Bonet F
氧化应激在心血管疾病的发生发展中起着重要作用，氧化应激被定义为相对于抗氧化剂防御产生过量的活性氧物种。内质网(ER)应激已成为ROS的一个重要来源，其调节可能具有心脏保护作用。此前，我们已经证明miR-16-5p在缺血性扩张型心肌病(ICM)患者的血浆中丰富，并在体外促进内质网应激诱导的心肌细胞凋亡。在这里，我们假设miR-16-5p可能通过内质网应激诱导氧化应激，靶向miR-16-5p可能在内质网应激介导的心脏损伤中发挥心脏保护作用。对ICM患者血浆中氧化标志物的分析表明，氧化应激与ICM有关。此外，我们证实miR-16-5p的过表达促进了AC16成肌细胞的氧化应激。我们还发现，在衣霉素诱导的内质网应激反应中，miR-16-5p抑制通过激活ATF6介导的细胞保护途径减少了细胞凋亡、炎症和心脏损伤。最后，通过双荧光素酶报告基因分析，确定ATF6是miR-16-5p的直接靶基因。我们的结果表明miR-16-5p通过调节ATF6促进了心肌细胞的内质网应激和氧化应激，提示抑制miR-16-5p有可能作为一种治疗手段来保护心脏免受内质网和氧化应激所致的损伤。
Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidative stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative stress-induced injury.
登录
查看更多内容
影响因子：
5.9
作者：
Calderon-Dominguez, Maria;Mangas, Alipio;Toro, Rocio
通讯作者：
Toro, Rocio
ATF6 上调 XBP1S 并抑制骨关节炎软骨中 ER 应激介导的细胞凋亡
影响因子：
4.8
作者：
Guo, Feng-Jin;Xiong, Zhangyuan;Jiang, Rong
通讯作者：
Jiang, Rong
影响因子：
2.6
作者：
BAMFORTH, CW
通讯作者：
BAMFORTH, CW
影响因子：
20.1
作者：
Cesselli, D;Jakoniuk, I;Anversa, P
通讯作者：
Anversa, P
影响因子：
3.1
作者：
Callis, Thomas E.;Chen, Jian-Fu;Wan, Da-Zhi
通讯作者：
Wan, Da-Zhi