Inhibition of Sestrin2 overexpression in diabetic cardiomyopathy ameliorates cardiac injury via restoration of mitochondrial function

Abstract

Mitochondrial dysfunction-induced apoptosis plays a crucial role in the progression of diabetic cardiomyopathy (DCM). Sestrin2 is an important oxidative stress response protein and is involved in the maintenance of mitochondrial function, especially under stress. The aim of the present study was to investigate the role of Sestrin2 in DCM and to explore the underlying mechanisms. H9c2 cardiomyocytes were induced with high glucose (HG) medium (33 mmol/l glucose) for an in vitro DCM model. C57BL/6 mice were induced for the in vivo DCM model by intraperitoneal streptozotocin injection. H9c2 cardiomyocytes were exposed to HG and infected with lentiviruses to express Sestrin2 short hairpin RNA (shRNA). The study found that cell viability and mitochondrial function were impaired while cell apoptosis and oxidative stress were increased in DCM. Sestrin2 was significantly upregulated in myocardial tissues of DCM mice and H9c2 cardiomyocytes in HG conditions. Downregulation of Sestrin2 increased cell viability, decreased cell apoptosis, and attenuated oxidative stress in H9c2 cells exposed to HG. Moreover, HG-induced mitochondrial injury was alleviated by Sestrin2 silencing. In conclusion, our finding indicated that the inhibition of enhanced Sestrin2 expression ameliorates cardiac injury in DCM, which might be largely attributed to the restoration of mitochondrial function.

Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP pathway

“…Sestrin2, a conserved antioxidant and metabolic regulator, markedly reprogram intracellular signaling pathways [25]. Currently, Sestrin2 was extensively explored in multi-diseases, such as diabetic cardiomyopathy, cholestatic liver injury, idiopathic pulmonary fibrosis, cancers [5,[26][27][28].…”

Sestrin2 in diabetes and diabetic complications

“…reported that Sestrin2 may enhance antioxidative actions and alleviate mitochondrial lesion by interacting with Nrf2 to prevent the diabetic rat heart from ischemia/reperfusion injury ( 18 ). Our previous research showed that inhibition of enhanced Sestrin2 expression attenuates cardiac injury in DCM, which may be mainly attributed to the restoration of mitochondrial function ( 127 ). Some antiglycemic agents, such as metformin and empagliflozin, were found to be cardioprotective through Sestrin2-associated mechanism.…”

Oxidative Stress-Induced Protein of SESTRIN2 in Cardioprotection Effect

“…However, other academics have a different viewpoint. Zhang et al [56] recently set out to investigate the role of SESTRIN2 in diabetic cardiomyopathy using H9C2 cardiomyocytes and DCM-induced C57BL/6 mice. Their findings suggest that inhibiting SESTRIN2 expression improves cardiac dysfunction in DCM, possibly due to the restoration of mitochondrial dysfunction-induced apoptosis.…”