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NADPH oxidase mediates oxidative stress and ventricular remodeling through SIRT3/FOXO3a pathway in diabetic mice

QiU, Jiuchun, Liu, Daiqi, Li, Pengsha, Zhou, Lingling, Zhou, Lu, Liang, Xing, Zhang, Yue, Yuan, Meng, Tse, Gary, Li, Guangping, and others. (2022) NADPH oxidase mediates oxidative stress and ventricular remodeling through SIRT3/FOXO3a pathway in diabetic mice. Antioxidants, 11 (9). Article Number 1745. E-ISSN 2076-3921. (doi:10.3390/antiox11091745) (KAR id:98706)


Oxidative stress and mitochondrial dysfunction are important mechanisms of ventricular remodeling, predisposed to the development of diabetic cardiomyopathy (DCM) in type 2 diabetes mellitus. In this study, we have successfully established a model of type 2 diabetes using a high-fat diet (HFD) in combination with streptozotocin (STZ). The mice were divided into three groups of six at random: control, diabetes, and diabetes with apocynin and the H9c2 cell line was used as an in vitro model for investigation. We examined the molecular mechanisms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation on mitochondrial dysfunction and ventricular remodeling in the diabetic mouse model. Hyperglycemia-induced oxidative stress led to a reduced expression of sirtuin 3 (SIRT3), thereby promoting forkhead box class O 3a (FOXO3a) acetylation in ventricular tissue and H9c2 cells. Reactive oxygen species (ROS) overproduction promoted ventricular structural modeling and conduction defects. These alterations were mitigated by inhibiting NADPH oxidase with the pharmaceutical drug apocynin (APO). Apocynin improved SIRT3 and Mn-SOD expression in H9c2 cells transfected with SIRT3 siRNA. In our diabetic mouse model, apocynin improved myocardial mitochondrial function and ROS overproduction through the recovery of the SIRT3/FOXO3a pathway, thereby reducing ventricular remodeling and the incidence of DCM.

Item Type: Article
DOI/Identification number: 10.3390/antiox11091745
Uncontrolled keywords: NADPH oxidase; oxidative stress; diabetic cardiomyopathy
Subjects: R Medicine > R Medicine (General)
Divisions: Divisions > Division of Natural Sciences > Kent and Medway Medical School
Depositing User: Manfred Gschwandtner
Date Deposited: 05 Dec 2022 18:29 UTC
Last Modified: 07 Dec 2022 17:32 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Liang, Xing.

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Tse, Gary.

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