Hydrogen Sulfide Induces Keap1 S-sulfhydration and Suppresses Diabetes-Accelerated Atherosclerosis via Nrf2 Activation
-
- Liping Xie
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China
-
- Yue Gu
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
-
- Mingliang Wen
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
-
- Shuang Zhao
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
-
- Wan Wang
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
-
- Yan Ma
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
-
- Guoliang Meng
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
-
- Yi Han
- Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
-
- Yuhui Wang
- Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China
-
- George Liu
- Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China
-
- Philip K. Moore
- Department of Pharmacology, National University of Singapore, Singapore, Singapore
-
- Xin Wang
- Faculty of Life Sciences, The University of Manchester, Manchester, U.K.
-
- Hong Wang
- Center for Metabolic Disease Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA
-
- Zhiren Zhang
- The Third Affiliated Hospital of Harbin Medical University, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China
-
- Ying Yu
- Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
-
- Albert Ferro
- Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, London, U.K.
-
- Zhengrong Huang
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China
-
- Yong Ji
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China
書誌事項
- 公開日
- 2016-06-22
- 権利情報
-
- http://www.diabetesjournals.org/content/license
- DOI
-
- 10.2337/db16-0020
- 公開者
- American Diabetes Association
この論文をさがす
説明
<jats:p>Hydrogen sulfide (H2S) has been shown to have powerful antioxidative and anti-inflammatory properties that can regulate multiple cardiovascular functions. However, its precise role in diabetes-accelerated atherosclerosis remains unclear. We report here that H2S reduced aortic atherosclerotic plaque formation with reduction in superoxide (O2−) generation and the adhesion molecules in streptozotocin (STZ)-induced LDLr−/− mice but not in LDLr−/−Nrf2−/− mice. In vitro, H2S inhibited foam cell formation, decreased O2− generation, and increased nuclear factor erythroid 2–related factor 2 (Nrf2) nuclear translocation and consequently heme oxygenase 1 (HO-1) expression upregulation in high glucose (HG) plus oxidized LDL (ox-LDL)–treated primary peritoneal macrophages from wild-type but not Nrf2−/− mice. H2S also decreased O2− and adhesion molecule levels and increased Nrf2 nuclear translocation and HO-1 expression, which were suppressed by Nrf2 knockdown in HG/ox-LDL–treated endothelial cells. H2S increased S-sulfhydration of Keap1, induced Nrf2 dissociation from Keap1, enhanced Nrf2 nuclear translocation, and inhibited O2− generation, which were abrogated after Keap1 mutated at Cys151, but not Cys273, in endothelial cells. Collectively, H2S attenuates diabetes-accelerated atherosclerosis, which may be related to inhibition of oxidative stress via Keap1 sulfhydrylation at Cys151 to activate Nrf2 signaling. This may provide a novel therapeutic target to prevent atherosclerosis in the context of diabetes.</jats:p>
収録刊行物
-
- Diabetes
-
Diabetes 65 (10), 3171-3184, 2016-06-22
American Diabetes Association
