microRNA-340-5p inhibits hypoxia/reoxygenation-induced apoptosis and oxidative stress in cardiomyocytes by regulating the Act1/NF-κB pathway.

Abstract

MicroRNAs (miRNAs) have been reported to play critical roles in the occurrence, progression, and treatment of many cardiovascular diseases. However, the molecular mechanism by which miRNA regulates target gene expression in ischemia-reperfusion (I/R) injury in acute myocardial infarction (AMI) is not entirely clear. MiR-340-5p was reported to be downregulated in acute ischemic stroke. However, it still remains unknown whether miR-340-5p is mediated in the pathogenesis process of I/R injury after AMI. In the present study, male C57BL/6 J mice and H9C2 cardiomyocytes were used as experimental models. Real-time polymerase chain reaction analysis, Western blot analysis, and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling immunofluorescence staining assay were conducted to examine related indicators in the study. We confirmed that the expression of miR-340-5p is downregulated after I/R in AMI mice and hypoxia/reperfusion (H/R)-induced cardiomyocytes. miR-340-5p could inhibit apoptosis and oxidative stress in H/R-induced H9C2 cells via downregulating activator 1 (Act1). The inhibiting action of miR-340-5p on H/R-induced apoptosis and oxidative stress in cardiomyocytes was partially reversed after Act1 overexpression. Moreover, the results showed that the NF-κB pathway may be mediated in the role of miR-340-5p on H/R-induced cardiomyocyte apoptosis and oxidative stress. We demonstrated that upregulation of miR-340-5p suppresses apoptosis and oxidative stress induced by H/R in H9C2 cells by inhibiting Act1. Therapeutic strategies that target miR-340-5p, Act1, and the NF-κB pathway could be beneficial for the treatment of I/R injury after AMI.

• Authors: Dong Li, Jian Zhou, Baoping Yang, Yan Yu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 9 Pg. 14618-14627 (09 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30989715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• MIRN340 microRNA, mouse
• MIRN340-1 microRNA, rat
• MicroRNAs
• NF-kappa B
• Replication Protein C

Topics

• Animals
• Apoptosis
• Cell Hypoxia
• Cell Line
• Disease Models, Animal
• Down-Regulation
• Male
• Mice
• MicroRNAs (genetics)
• Myocardial Reperfusion Injury (genetics, metabolism)
• Myocytes, Cardiac (cytology)
• NF-kappa B (metabolism)
• Oxidative Stress
• Rats
• Replication Protein C (genetics)
• Signal Transduction