{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825895629790464.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2337/db16-0020"}},{"identifier":{"@type":"URI","@value":"http://diabetes.diabetesjournals.org/syndication/doi/10.2337/db16-0020"}},{"identifier":{"@type":"URI","@value":"https://journals.org/diabetes/diabetes/article-pdf/65/10/3171/580325/db160020.pdf"}},{"identifier":{"@type":"URI","@value":"https://diabetesjournals.org/diabetes/article-pdf/65/10/3171/580325/db160020.pdf"}}],"dc:title":[{"@value":"Hydrogen Sulfide Induces Keap1 S-sulfhydration and Suppresses Diabetes-Accelerated Atherosclerosis via Nrf2 Activation"}],"description":[{"type":"abstract","notation":[{"@value":"<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>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382825895629790470","@type":"Researcher","foaf:name":[{"@value":"Liping Xie"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China"},{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790468","@type":"Researcher","foaf:name":[{"@value":"Yue Gu"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790595","@type":"Researcher","foaf:name":[{"@value":"Mingliang Wen"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790474","@type":"Researcher","foaf:name":[{"@value":"Shuang Zhao"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790466","@type":"Researcher","foaf:name":[{"@value":"Wan Wang"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790475","@type":"Researcher","foaf:name":[{"@value":"Yan Ma"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790467","@type":"Researcher","foaf:name":[{"@value":"Guoliang Meng"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790472","@type":"Researcher","foaf:name":[{"@value":"Yi Han"}],"jpcoar:affiliationName":[{"@value":"Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790476","@type":"Researcher","foaf:name":[{"@value":"Yuhui Wang"}],"jpcoar:affiliationName":[{"@value":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790593","@type":"Researcher","foaf:name":[{"@value":"George Liu"}],"jpcoar:affiliationName":[{"@value":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790592","@type":"Researcher","foaf:name":[{"@value":"Philip K. Moore"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology, National University of Singapore, Singapore, Singapore"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790464","@type":"Researcher","foaf:name":[{"@value":"Xin Wang"}],"jpcoar:affiliationName":[{"@value":"Faculty of Life Sciences, The University of Manchester, Manchester, U.K."}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790473","@type":"Researcher","foaf:name":[{"@value":"Hong Wang"}],"jpcoar:affiliationName":[{"@value":"Center for Metabolic Disease Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790469","@type":"Researcher","foaf:name":[{"@value":"Zhiren Zhang"}],"jpcoar:affiliationName":[{"@value":"The Third Affiliated Hospital of Harbin Medical University, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790594","@type":"Researcher","foaf:name":[{"@value":"Ying Yu"}],"jpcoar:affiliationName":[{"@value":"Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790471","@type":"Researcher","foaf:name":[{"@value":"Albert Ferro"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, London, U.K."}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790465","@type":"Researcher","foaf:name":[{"@value":"Zhengrong Huang"}],"jpcoar:affiliationName":[{"@value":"Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825895629790596","@type":"Researcher","foaf:name":[{"@value":"Yong Ji"}],"jpcoar:affiliationName":[{"@value":"Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, China"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00121797"},{"@type":"EISSN","@value":"1939327X"}],"prism:publicationName":[{"@value":"Diabetes"}],"dc:publisher":[{"@value":"American Diabetes Association"}],"prism:publicationDate":"2016-06-22","prism:volume":"65","prism:number":"10","prism:startingPage":"3171","prism:endingPage":"3184"},"reviewed":"false","dc:rights":["http://www.diabetesjournals.org/content/license"],"url":[{"@id":"http://diabetes.diabetesjournals.org/syndication/doi/10.2337/db16-0020"},{"@id":"https://journals.org/diabetes/diabetes/article-pdf/65/10/3171/580325/db160020.pdf"},{"@id":"https://diabetesjournals.org/diabetes/article-pdf/65/10/3171/580325/db160020.pdf"}],"createdAt":"2016-06-24","modifiedAt":"2022-11-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004233983613824","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Hydrogen sulfide inhibits NLRP3 inflammasome activation and reduces cytokine production both in vitro and in a mouse model of 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