Dapagliflozin attenuates high glucose-and hypoxia/reoxygenation-induced injury via activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy in H9c2 cardiomyocytes

Tu, Weiling1; Li, Liang2; Yi, Ming3; Chen, Junyu4; Wang, Xiaoqing4,6; Sun, Yan5,7

2023-09-01

10.1080/13813455.2023.2252200

ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY   影响因子和分区

1381-3455

1744-4160

This study investigated the protective effect of dapagliflozin on H9c2 cardiomyocyte function under high glucose and hypoxia/reoxygenation (HG-H/R) conditions and identified the underlying molecular mechanisms. Dapagliflozin reduced the level of lactate dehydrogenase and reactive oxygen species in cardiomyocytes under HG-H/R conditions and was accompanied by a decrease in caspase-3/9 activity. In addition, Dapagliflozin significantly reduced mitochondrial permeability transition pore opening and increased ATP content, accompanied by upregulation of OPA1 with autophagy-related protein molecules and activation of the AMPK/mTOR signalling pathway in HG-H/R treated cardiomyocytes. OPA1 knockdown or compound C treatment attenuated the protective effects of dapagliflozin on the cardiomyocytes under HG-H/R conditions. Downregulation of OPA1 expression increased mitochondrial intolerance in cardiomyocytes during HG-H/R injury and the AMPK-mTOR-autophagy signalling is a key mechanism for protecting mitochondrial function and reducing cardiomyocyte apoptosis. Collectively, dapagliflozin exerted protective effects on the cardiomyocytes under HG-H/R conditions. Dapagliflozin attenuated myocardial HG-H/R injury by activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy.

Diabetic myocardial ischaemia-reperfusion cardiomyocytes dapagliflozin OPA1 mitochondrial autophagy

SCI

英语

通讯

Baoan District of Shenzhen Science and Technology Plan Basic Research Project[2020JD479] ; Fund of Sanming Project of Medicine in Shenzhen[SZSM201911017] ; Nanshan District of Healthcare Science and Technology Project[NS2022144]

Biochemistry & Molecular Biology ; Biophysics ; Endocrinology & Metabolism ; Physiology

Biochemistry & Molecular Biology ; Biophysics ; Endocrinology & Metabolism ; Physiology

WOS:001056918400001

TAYLOR & FRANCIS LTD

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Jiangxi Prov Peoples Hosp, Affiliated Hosp 1, Dept Gynecol, Nanchang Med Coll, Nanchang, Peoples R China
2.Guangzhou Univ Chinese Med, Shenzhen Baoan Tradit Chinese Med Hosp, Dept Cardiol, Shenzhen, Peoples R China
3.Hunan Univ Chinese Med, Affiliated Integrated Chinese & Western Med Hosp 2, Liuyang Hosp Tradit Chinese Med, Dept Cardiol, Liuyang, Peoples R China
4.Chinese Acad Med Sci, Shenzhen Sun Yat Sen Cardiovasc Hosp, Fuwai Hosp, Dept Cardiol, Shenzhen, Peoples R China
5.Southern Univ Sci & Technol Hosp, Dept Endocrinol, Shenzhen, Peoples R China
6.Chinese Acad Med Sci, Fuwai Hosp, Shenzhen Sun Yat Sen Cardiovasc Hosp, Dept Cardiol, Shenzhen 518057, Peoples R China
7.Southern Univ Sci, Technol Hosp, Dept Endocrinol, Shenzhen 518101, Peoples R China

Tu, Weiling,Li, Liang,Yi, Ming,et al. Dapagliflozin attenuates high glucose-and hypoxia/reoxygenation-induced injury via activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy in H9c2 cardiomyocytes[J]. ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY,2023.

Tu, Weiling,Li, Liang,Yi, Ming,Chen, Junyu,Wang, Xiaoqing,&Sun, Yan.(2023).Dapagliflozin attenuates high glucose-and hypoxia/reoxygenation-induced injury via activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy in H9c2 cardiomyocytes.ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY.

Tu, Weiling,et al."Dapagliflozin attenuates high glucose-and hypoxia/reoxygenation-induced injury via activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy in H9c2 cardiomyocytes".ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY (2023).