Abstract
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 ≥ 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.
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Acknowledgments
This work was supported by the National Basic Research Program of China (973 program, 2013CB531104), the Key Project of National Science Foundation of China (81130088), and the National Natural Science Foundation of China (81100072).
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Lu Wang and Ye Yuan contributed equally to this article.
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Wang, L., Yuan, Y., Li, J. et al. MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional modification of the antioxidant network. Cell Stress and Chaperones 20, 411–420 (2015). https://doi.org/10.1007/s12192-014-0565-9
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DOI: https://doi.org/10.1007/s12192-014-0565-9