| Title | Hydrogen Sulfide Induces Keap1 S-sulfhydration and Suppresses Diabetes-Accelerated Atherosclerosis via Nrf2 Activation |
| Authors | Xie, Liping Gu, Yue Wen, Mingliang Zhao, Shuang Wang, Wan Ma, Yan Meng, Guoliang Han, Yi Wang, Yuhui Liu, George Moore, Philip K. Wang, Xin Wang, Hong Zhang, Zhiren Yu, Ying Ferro, Albert Huang, Zhengrong Ji, Yong |
| Affiliation | Xiamen Univ, Affiliated Hosp 1, Dept Cardiol, Xiamen, Peoples R China. Nanjing Med Univ, Atherosclerosis Res Ctr, Collaborat Innovat Ctr Cardiovasc Dis Translat Me, Nanjing, Jiangsu, Peoples R China. Nanjing Med Univ, Affiliated Hosp 1, Dept Geriatr, Nanjing, Jiangsu, Peoples R China. Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing, Peoples R China. Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing, Peoples R China. Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore. Univ Manchester, Fac Life Sci, Manchester, Lancs, England. Temple Univ, Dept Pharmacol, Sch Med, Ctr Metab Dis Res, Philadelphia, PA 19122 USA. Harbin Med Univ, Inst Metab Dis, Affiliated Hosp 3, Heilongjiang Acad Med Sci, Harbin, Peoples R China. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. Kings Coll London, British Heart Fdn, Ctr Res Excellence, Dept Clin Pharmacol,Cardiovasc Div, London, England. Xiamen Univ, Affiliated Hosp 1, Dept Cardiol, Xiamen, Peoples R China. Ji, Y (reprint author), Nanjing Med Univ, Atherosclerosis Res Ctr, Collaborat Innovat Ctr Cardiovasc Dis Translat Me, Nanjing, Jiangsu, Peoples R China. |
| Keywords | VEIN ENDOTHELIAL-CELLS NITRIC-OXIDE SYNTHASE OXIDATIVE STRESS DEPENDENT MANNER COMPLICATIONS MICE INFLAMMATION MACROPHAGE PROTECTS PATHWAY |
| Issue Date | 2016 |
| Publisher | DIABETES |
| Citation | DIABETES.2016,65(10),3171-3184. |
| Abstract | 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 (O-2(-)) 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 O-2(-) 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 O-2(-) 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 O-2(-) 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. |
| URI | http://hdl.handle.net/20.500.11897/493630 |
| ISSN | 0012-1797 |
| DOI | 10.2337/db16-0020 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
