Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling
Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-04-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323171730561X |
| _version_ | 1811287969610334208 |
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| author | Shih-Hung Chan Ching-Hsia Hung Jhih-Yuan Shih Pei-Ming Chu Yung-Hsin Cheng Huei-Chen Lin Pei-Ling Hsieh Kun-Ling Tsai |
| author_facet | Shih-Hung Chan Ching-Hsia Hung Jhih-Yuan Shih Pei-Ming Chu Yung-Hsin Cheng Huei-Chen Lin Pei-Ling Hsieh Kun-Ling Tsai |
| author_sort | Shih-Hung Chan |
| collection | DOAJ |
| description | Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-κB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation. Keywords: Sirtuin 1, Coronary artery disease, Hyperhomocysteinemia, Oxidative stress |
| first_indexed | 2024-04-13T03:27:47Z |
| format | Article |
| id | doaj.art-e621815267c54fc38c0c47354a84b252 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T03:27:47Z |
| publishDate | 2018-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-e621815267c54fc38c0c47354a84b2522022-12-22T03:04:36ZengElsevierRedox Biology2213-23172018-04-0114116125Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signalingShih-Hung Chan0Ching-Hsia Hung1Jhih-Yuan Shih2Pei-Ming Chu3Yung-Hsin Cheng4Huei-Chen Lin5Pei-Ling Hsieh6Kun-Ling Tsai7Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Internal Medicine, Chi-Mei Hospital, Tainan, TaiwanDepartment of Anatomy, School of Medicine, China Medical University, Taichung, TaiwanDepartment of Education and Research, Taipei City Hospital, Taipei, TaiwanInstitute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Physical Therapy, Shu-Zen Junior College of Medicine and Management, TaiwanInstitute of Oral Sciences, Chung Shan Medical University, Taichung, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Corresponding author.Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-κB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation. Keywords: Sirtuin 1, Coronary artery disease, Hyperhomocysteinemia, Oxidative stresshttp://www.sciencedirect.com/science/article/pii/S221323171730561X |
| spellingShingle | Shih-Hung Chan Ching-Hsia Hung Jhih-Yuan Shih Pei-Ming Chu Yung-Hsin Cheng Huei-Chen Lin Pei-Ling Hsieh Kun-Ling Tsai Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling Redox Biology |
| title | Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling |
| title_full | Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling |
| title_fullStr | Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling |
| title_full_unstemmed | Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling |
| title_short | Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling |
| title_sort | exercise intervention attenuates hyperhomocysteinemia induced aortic endothelial oxidative injury by regulating sirt1 through mitigating nadph oxidase lox 1 signaling |
| url | http://www.sciencedirect.com/science/article/pii/S221323171730561X |
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