title: Carbon monoxide ameliorates hepatic ischemia/reperfusion injury via sirtuin 1-mediated deacetylation of high-mobility group box 1 in rats.
abstract: Carbon monoxide (CO) exerts protective effects on hepatic ischemia/reperfusion injury (IRI), but the underlying molecular mechanisms are not fully understood. High-mobility group box 1 (HMGB1) is an important mediator of injury and inflammation in hepatic IRI. Here, we investigated whether CO could attenuate hepatic IRI via inhibition of HMGB1 release, particularly through sirtuin 1 (SIRT1). CO was released by treatment with carbon monoxide-releasing molecule (CORM)-2. CORM-2-delivered CO ameliorated hepatic IRI, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory responses, and less severe ischemia/reperfusion-associated histopathologic changes. Treatment with CORM-2 significantly inhibited IRI-induced HMGB1 translocation and release. SIRT1 expression was increased by CORM-2 pretreatment. When CORM-2-induced SIRT1 expression was inhibited using EX527, HMGB1 translocation and release were increased and hepatic IRI was worsened, whereas SIRT1 activation by resveratrol reversed this trend. In vitro, CORM-2 reduced hypoxia/reoxygenation-induced HMGB1 translocation and release, these inhibitions were blocked by SIRT1 inhibition using EX527 or SIRT1 small interfering RNA both in alpha mouse liver 12 cells and RAW264.7 macrophages. Moreover, SIRT1 directly interacted with and deacetylated HMGB1. IRI increased HMGB1 acetylation, which was abolished by CORM-2 treatment via SIRT1. In conclusion, these results suggest that CO may increase SIRT1 expression, which may decrease HMGB1 acetylation and subsequently reduce its translocation and release, thereby protecting against hepatic IRI. Liver Transplantation 23 510-526 2017 AASLD.
authors.affiliation: Department of Biliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Enshuang
authors.initials: E
authors.lastname: Guo
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shenpei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jifa
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
authors.affiliation: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Wuhan, China.|Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002248:Carbon Monoxide / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D009942:Organometallic Compounds; D020011:Protective Agents; D013267:Stilbenes; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol