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MiR-486 regulates cardiomyocyte apoptosis by p53-mediated BCL-2 associated mitochondrial apoptotic pathway
Yuhan Sun1, Qiang Su1, Lang Li2
1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Background:
Cardiomyocyte apoptosis is a common pathological manifestation that occurs in several heart diseases. This study aimed to explore the mechanism of microRNA-486 (miR-486) in cardiomyocyte apoptosis by interfering with the p53-activated BCL-2 associated mitochondrial pathway.
Methods:
miR-486 mimics and inhibitors were transfected into the primary cardiomyocytes of suckling Sprague-Dawley rat pups, and H2O2 was used to induce apoptosis. Flow cytometry and TUNEL were both used to detect cardiomyocyte apoptosis, while the relative mRNA transcript and protein levels of miR-486, p53, Bbc3, BCL-2, and cleaved caspase-3 were detected using RT-PCR and western blot analysis, respectively.
Results:
miR-486 overexpression significantly decreased the expressions of p53, Bbc3 and cleaved caspase-3 (P < 0.05), and BCL-2 expression was significantly increased (P < 0.05), which in turn caused a significant decrease in the rate of cardiomyocyte apoptosis (P < 0.05). In contrast, miR-486 silencing resulted in an elevated rate of cardiomyocyte apoptosis (P < 0.05).
Conclusion:
miR-486 may regulate cardiomyocyte apoptosis via p53-mediated BCL-2 associated mitochondrial apoptotic pathway. Therefore, up-regulating miR-486 expression in cardiomyocytes can effectively reduce the activation of the BCL-2 associated mitochondrial apoptotic pathway, consequently protecting cardiomyocytes.
Insights
MicroRNA-486 (miR-486) protects heart cells by inhibiting the p53-activated BCL-2 mitochondrial pathway. Upregulating miR-486 reduces cardiomyocyte apoptosis, offering a potential therapeutic strategy for heart disease.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Cardiomyocyte apoptosis is a critical factor in various heart diseases.
- Understanding the molecular mechanisms regulating cardiomyocyte apoptosis is essential for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA-486 (miR-486) in regulating cardiomyocyte apoptosis.
- To elucidate the involvement of the p53-activated BCL-2 associated mitochondrial pathway in miR-486's function.
Main Methods:
- Primary cardiomyocytes were transfected with miR-486 mimics or inhibitors.
- Hydrogen peroxide (H2O2) was used to induce apoptosis in cardiomyocytes.
- Flow cytometry, TUNEL assay, RT-PCR, and Western blot were employed to assess apoptosis rates and molecular changes.
Main Results:
- miR-486 overexpression significantly reduced p53, Bbc3, and cleaved caspase-3 expression while increasing BCL-2 levels.
- Overexpression of miR-486 led to a significant decrease in cardiomyocyte apoptosis.
- Silencing miR-486 resulted in an elevated rate of cardiomyocyte apoptosis.
Conclusions:
- miR-486 regulates cardiomyocyte apoptosis through the p53-mediated BCL-2 associated mitochondrial pathway.
- Increasing miR-486 expression in cardiomyocytes can protect them by inhibiting this apoptotic pathway.
- miR-486 represents a potential therapeutic target for mitigating heart disease-related cardiomyocyte loss.
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