Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK

Emerging evidence demonstrated dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, prevented various cardiovascular events. However, the detailed mechanisms underlying its cardioprotective properties remained largely unknown. In the present study, we sought to investigate the effects o...

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Bibliographic Details
Published in:Cell & bioscience 2021-02, Vol.11 (1), p.44-44, Article 44
Main Authors: Tsai, Kun-Ling, Hsieh, Pei-Ling, Chou, Wan-Ching, Cheng, Hui-Ching, Huang, Yu-Ting, Chan, Shih-Hung
Format: Article
Language:English
Subjects:
Adenosine
AMPK
Antibodies
Apoptosis
Cardiac function
Copy number
Coronary vessels
Dapagliflozin
Dehydrogenases
Dextrose
Echocardiography
Ethylenediaminetetraacetic acid
Glucose
Heart attacks
Hypoxia
Ischemia
Ischemia/reperfusion injury
Kinases
Laboratory animals
Membrane potential
Membranes
Metabolism
Mitochondrial DNA
Myoblasts
Myocardial infarction
Myocardium
Na+/glucose cotransporter
NAD(P)H oxidase
Ostomy
Oxidases
Oxidative stress
Penicillin
Phosphorylation
Prevention
Protein kinase C
Proteins
Reperfusion
Type 2 diabetes
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Summary:Emerging evidence demonstrated dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, prevented various cardiovascular events. However, the detailed mechanisms underlying its cardioprotective properties remained largely unknown. In the present study, we sought to investigate the effects of DAPA on the cardiac ischemia/reperfusion (I/R) injury. Results from in vitro experiments showed that DAPA induced the phosphorylation of AMPK, resulting in the downregulation of PKC in the cardiac myoblast H9c2 cells following hypoxia/reoxygenation (H/R) condition. We demonstrated that DAPA treatment diminished the H/R-elicited oxidative stress via the AMPK/ PKC/ NADPH oxidase pathway. In addition, DAPA prevented the H/R-induced abnormality of PGC-1α expression, mitochondrial membrane potential, and mitochondrial DNA copy number through AMPK/ PKC/ NADPH oxidase signaling. Besides, DAPA reversed the H/R-induced apoptosis. Furthermore, we demonstrated that DAPA improved the I/R-induced cardiac dysfunction by echocardiography and abrogated the I/R-elicited apoptosis in the myocardium of rats. Also, the administration of DAPA mitigated the production of myocardial infarction markers. In conclusion, our data suggested that DAPA treatment holds the potential to ameliorate the I/R-elicited oxidative stress and the following cardiac apoptosis via modulation of AMPK, which attenuates the cardiac dysfunction caused by I/R injury.
ISSN:2045-3701
2045-3701
DOI:10.1186/s13578-021-00547-y