TY - JOUR
T1 - Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK
AU - Tsai, Kun Ling
AU - Hsieh, Pei Ling
AU - Chou, Wan Ching
AU - Cheng, Hui Ching
AU - Huang, Yu Ting
AU - Chan, Shih Hung
N1 - Funding Information:
This study was supported by Ministry of Science and Technology, Taiwan (MOST-108-2320-B-006 -053) and National Cheng Kung University Hospital, Taiwan (NCKUH-10902010).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: 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. Results: 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. Conclusions: 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.
AB - Background: 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. Results: 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. Conclusions: 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.
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U2 - 10.1186/s13578-021-00547-y
DO - 10.1186/s13578-021-00547-y
M3 - Article
AN - SCOPUS:85101780476
SN - 2045-3701
VL - 11
JO - Cell and Bioscience
JF - Cell and Bioscience
IS - 1
M1 - 44
ER -