MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional modification of the antioxidant network

作者：Wang, Lu; Yuan, Ye; Li, Jing; Ren, Hequn; Cai, Qingxin; Chen, Xu; Liang, Haihai; Shan, Hongli; Fu, Zidong Donna; Gao, Xu; Lv, Yanjie; Yang, Baofeng^*; Zhang, Yan

来源：Cell Stress & Chaperones, 2015, 20(3): 411-420.

DOI：10.1007/s12192-014-0565-9

• MicroRNAs
• Oxidative stress
• Post-transcriptional modification

Oxidative stress plays an important role in cardiovascular diseases. Studies have shown that miR-1 plays an important role in the regulation of cardiomyocyte apoptosis, which can be the result of oxidative stress. This study was designed to determine whether increased miR-1 levels lead to alterations in the expression of proteins related to oxidative stress, which could contribute to heart dysfunction. We compared cardiac function in wild-type (WT) and miR-1 transgene (miR-1/Tg) C57BL/6 mice (n a parts per thousand yenaEuro parts per thousand 10/group). Echocardiography showed that stroke volume (SV), ejection fraction (EF), and fractional shortening (FS) were significantly decreased in miR-1/Tg mice. Concomitantly, the level of reactive oxygen species (ROS) was elevated in the cardiomyocytes from the miR-1/Tg mice, and activities of lactate dehydrogenase (LDH) and creatinine kinase (CK) in plasma were also increased in the miR-1/Tg mice. All of these changes could be reversed by LNA-anti-miR-1. In the cardiomyocytes of neonatal Wistar rats, overexpression of miR-1 exhibits higher ROS levels and lower resistance to H2O2-induced oxidative stress. We demonstrated that SOD1, Gclc, and G6PD are novel targets of miR-1 for post-transcriptional repression. MicroRNA-1 post-transcriptionally represses the expression of SOD1, Gclc, and G6PD, which is likely to contribute to the increased ROS level and the susceptibility to oxidative stress of the hearts of miR-1 transgenic mice.

• 出版日期2015-5
• 单位哈尔滨医科大学