NADPH oxidase mediates oxidative stress and ventricular remodeling through SIRT3/FOXO3a pathway in diabetic mice
Journal article
Jiuchun Qiu, Daiqi Liu, Pengsha Li, Lingling Zhou, Lu Zhou, Xing Liu, Yue Zhang, Meng Yuan, Gary Tse, Guangping Li and Tong Liu 2022. NADPH oxidase mediates oxidative stress and ventricular remodeling through SIRT3/FOXO3a pathway in diabetic mice. Antioxidants. 11 (9), p. 1745. https://doi.org/10.3390/antiox11091745
Authors | Jiuchun Qiu, Daiqi Liu, Pengsha Li, Lingling Zhou, Lu Zhou, Xing Liu, Yue Zhang, Meng Yuan, Gary Tse, Guangping Li and Tong Liu |
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Abstract | 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. |
Keywords | NADPH; Oxidative stress; Diabetic cardiomyopathy |
Year | 2022 |
Journal | Antioxidants |
Journal citation | 11 (9), p. 1745 |
Publisher | MDPI |
ISSN | 2076-3921 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/antiox11091745 |
Official URL | https://www.mdpi.com/2076-3921/11/9/1745 |
Publication dates | |
02 Sep 2022 | |
Publication process dates | |
Accepted | 30 Aug 2022 |
Deposited | 24 May 2023 |
Publisher's version | License |
Output status | Published |
https://repository.canterbury.ac.uk/item/94q9z/nadph-oxidase-mediates-oxidative-stress-and-ventricular-remodeling-through-sirt3-foxo3a-pathway-in-diabetic-mice
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