PUBLICATION
Effect of AMPK-p53-klf2a Pathway in Hyperglycemia-induced Cardiac Remodeling in Adult Zebrafish
- Authors
- Wang, Q., Luo, C., Lu, G., Chen, Z.
- ID
- ZDB-PUB-200907-1
- Date
- 2020
- Source
- Journal of diabetes investigation 12(3): 320-333 (Journal)
- Registered Authors
- Keywords
- AMP-Activated Protein Kinases, Diabetic cardiomyopathies, Zebrafish
- MeSH Terms
-
- AMP-Activated Protein Kinases/metabolism
- Adenosine Monophosphate/metabolism
- Animals
- Apoptosis
- Diabetic Cardiomyopathies/metabolism*
- Hyperglycemia/metabolism*
- Kruppel-Like Transcription Factors/metabolism
- Signal Transduction*
- Zebrafish
- PubMed
- 32881390 Full text @ J Diabetes Investig
Citation
Wang, Q., Luo, C., Lu, G., Chen, Z. (2020) Effect of AMPK-p53-klf2a Pathway in Hyperglycemia-induced Cardiac Remodeling in Adult Zebrafish. Journal of diabetes investigation. 12(3):320-333.
Abstract
Introductions Diabetic cardiomyopathy is a type of myocardial disease. It causes left ventricular hypertrophy, followed by diastolic and systolic dysfunction, eventually leading to congestive heart failure. However, the underlying mechanism still requires further elucidation.
Materials and methods High glucose zebrafish model was constructed by administrating streptozocin intraperitoneally to enhance the development of cardiomyopathy, and then treated with AMPK activator. Cardiac structure and function, protein and gene expression were then analyzed. Cardiomyocytes culture in vitro using lentivirus were used for detection of AMPK, p53 and klf2a gene expression.
Results In the hyperglycemia group, ECG findings revealed arrhythmia, echocardiography results revealed heart enlargement and dysfunction, and many differences such as increased apoptosis, myocardial fiber loss were observed. The p-AMPK and klf2a expression were downregulated, and p53 expression was upregulated. Activation of p-AMPK reduced p53 and increased klf2a expression, alleviated apoptosis in cardiomyocytes and improved cardiac function in the hyperglycemic zebrafish. In vitro knockdown system of AMPK, p53 and klf2a using lentivirus illustrated an increased p53 expression and decreased klf2a expression in cardiomyocytes by inhibiting AMPK. Repression of p53 and up-regulation of klf2a expression were observed but no changes in the expression of AMPK and its phosphorylated type.
Conclutions In the model of STZ-induced hyperglycemia zebrafish, the reduction of phosphorylated AMPK increased p53, which led to KLF2a decrease to facilitate apoptosis of cardiomyocytes, inducing the cardiac remodeling and cardiac dysfunction. These results can be reversed by AMPK activator, which means AMPK-p53-klf2a pathway might be a potential target for DCM intervention.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping