NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice
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 co...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/9/1745 |
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| author | Jiuchun Qiu Daiqi Liu Pengsha Li Lingling Zhou Lu Zhou Xing Liu Yue Zhang Meng Yuan Gary Tse Guangping Li Tong Liu |
| author_facet | Jiuchun Qiu Daiqi Liu Pengsha Li Lingling Zhou Lu Zhou Xing Liu Yue Zhang Meng Yuan Gary Tse Guangping Li Tong Liu |
| author_sort | Jiuchun Qiu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:52:40Z |
| format | Article |
| id | doaj.art-319230a503234a37937d8ffab7ab5553 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:52:40Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-319230a503234a37937d8ffab7ab55532023-11-23T14:48:14ZengMDPI AGAntioxidants2076-39212022-09-01119174510.3390/antiox11091745NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic MiceJiuchun Qiu0Daiqi Liu1Pengsha Li2Lingling Zhou3Lu Zhou4Xing Liu5Yue Zhang6Meng Yuan7Gary Tse8Guangping Li9Tong Liu10Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, ChinaOxidative 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.https://www.mdpi.com/2076-3921/11/9/1745NADPH oxidaseoxidative stressdiabetic cardiomyopathy |
| spellingShingle | Jiuchun Qiu Daiqi Liu Pengsha Li Lingling Zhou Lu Zhou Xing Liu Yue Zhang Meng Yuan Gary Tse Guangping Li Tong Liu NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice Antioxidants NADPH oxidase oxidative stress diabetic cardiomyopathy |
| title | NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice |
| title_full | NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice |
| title_fullStr | NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice |
| title_full_unstemmed | NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice |
| title_short | NADPH Oxidase Mediates Oxidative Stress and Ventricular Remodeling through SIRT3/FOXO3a Pathway in Diabetic Mice |
| title_sort | nadph oxidase mediates oxidative stress and ventricular remodeling through sirt3 foxo3a pathway in diabetic mice |
| topic | NADPH oxidase oxidative stress diabetic cardiomyopathy |
| url | https://www.mdpi.com/2076-3921/11/9/1745 |
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