N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy
Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardiop...
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| Format: | Article |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/9257291 |
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| author | Sheng Wang Chunyan Wang Fuxia Yan Tingting Wang Yi He Haobo Li Zhengyuan Xia Zhongjun Zhang |
| author_facet | Sheng Wang Chunyan Wang Fuxia Yan Tingting Wang Yi He Haobo Li Zhengyuan Xia Zhongjun Zhang |
| author_sort | Sheng Wang |
| collection | DOAJ |
| description | Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p<0.05). Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI. |
| format | Article |
| id | doaj-art-5099b0bf9cf044bf8c76d384800d8bae |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-5099b0bf9cf044bf8c76d384800d8bae2025-02-03T06:44:20ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/92572919257291N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive AutophagySheng Wang0Chunyan Wang1Fuxia Yan2Tingting Wang3Yi He4Haobo Li5Zhengyuan Xia6Zhongjun Zhang7Department of Anesthesiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangdong, ChinaDepartment of Anesthesiology, Shenzhen People’s Hospital, Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College, Jinan University, Shenzhen, ChinaDepartment of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Anesthesiology, The University of Hong Kong, Pokfulam, Hong KongDepartment of Anesthesiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangdong, ChinaDepartment of Anesthesiology, The University of Hong Kong, Pokfulam, Hong KongDepartment of Anesthesiology, The University of Hong Kong, Pokfulam, Hong KongDepartment of Anesthesiology, Shenzhen People’s Hospital, Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College, Jinan University, Shenzhen, ChinaBackground. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p<0.05). Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI.http://dx.doi.org/10.1155/2017/9257291 |
| spellingShingle | Sheng Wang Chunyan Wang Fuxia Yan Tingting Wang Yi He Haobo Li Zhengyuan Xia Zhongjun Zhang N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy Mediators of Inflammation |
| title | N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy |
| title_full | N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy |
| title_fullStr | N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy |
| title_full_unstemmed | N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy |
| title_short | N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy |
| title_sort | n acetylcysteine attenuates diabetic myocardial ischemia reperfusion injury through inhibiting excessive autophagy |
| url | http://dx.doi.org/10.1155/2017/9257291 |
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