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Knockdown of SGLT1 prevents the apoptosis of cardiomyocytes induced by glucose fluctuation via relieving oxidative stress and mitochondrial dysfunction.
- Source :
-
Biochemistry and cell biology = Biochimie et biologie cellulaire [Biochem Cell Biol] 2021 Jun; Vol. 99 (3), pp. 356-363. Date of Electronic Publication: 2020 Dec 01. - Publication Year :
- 2021
-
Abstract
- Fluctuations in the concentration of glucose in the blood is more detrimental than a constantly high level of glucose with respect to the development of cardiovascular complications associated with diabetes mellitus (DM). Sodium glucose cotransporter 2 (SGLT2) inhibitors have been developed as antidiabetic drugs with cardiovascular benefits; however, whether inhibition of SGLT1 protects the diabetic heart remains to be determined. This study investigated the role of SGLT1 in rat H9c2 cardiomyocytes subjected to fluctuating levels of glucose and the underlying mechanisms. The results indicated that knockdown of SGLT1 restored cell proliferation and suppressed the cytotoxicity associated with fluctuating glucose levels. Oxidative stress was induced in H9c2 cells subjected to fluctuating glucose levels, but these changes were effectively reversed by knockdown of SGLT1, as manifested by reductions in the level of intracellular reactive oxygen species and increased antioxidant activity. Further study demonstrated that knockdown of SGLT1 attenuated the mitochondrial dysfunction in H9c2 cells exposed to fluctuating glucose levels, by restoring mitochondrial membrane potential and promoting mitochondrial fusion. In addition, knockdown of SGLT1 downregulated the expression of Bax, upregulated the expression of Bcl-2, and reduced the activation of caspase-3 in H9c2 cells subjected to fluctuating levels of glucose. Collectively, our results show that knockdown of SGLT1 ameliorates the apoptosis of cardiomyocyte caused by fluctuating glucose levels via regulating oxidative stress and combatting mitochondrial dysfunction.
- Subjects :
- Animals
Membrane Potential, Mitochondrial
Mitochondria metabolism
Mitochondria pathology
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Rats
Reactive Oxygen Species metabolism
Sodium-Glucose Transporter 1 genetics
Sodium-Glucose Transporter 1 metabolism
Apoptosis
Glucose pharmacology
Mitochondria drug effects
Myocytes, Cardiac drug effects
Oxidative Stress drug effects
Sodium-Glucose Transporter 1 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1208-6002
- Volume :
- 99
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemistry and cell biology = Biochimie et biologie cellulaire
- Publication Type :
- Academic Journal
- Accession number :
- 33259229
- Full Text :
- https://doi.org/10.1139/bcb-2020-0491