title: Decreased expression of sirtuin 6 is associated with release of high mobility group box-1 after cerebral ischemia.
abstract: Sirtuin 6 (SIRT6) belongs to the sirtuin family of NAD(+)-dependent deacetylases and has been implicated in the regulation of metabolism, inflammation, and aging. Here, we found that SIRT6 was predominantly expressed in neuronal cells throughout the entire brain. Ischemia models using transient middle cerebral artery occlusion in rats and oxygen/glucose deprivation (OGD) in SH-SY5Y neuronal cells showed that ischemia reduced SIRT6 expression and induced the release of high mobility group box-1 (HMGB1) from cell nuclei. The reduced expression of SIRT6 via treatment with SIRT6 siRNA dramatically enhanced the OGD-induced release of HMGB1 in SH-SY5Y cells. Together, our data suggest that SIRT6 may serve as a potential therapeutic target for HMGB1-mediated inflammation after cerebral ischemia.
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul 120-752, Republic of Korea.
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Lee
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Kim
authors.forename: Hyunji
authors.initials: H
authors.lastname: Lee
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Youngsok
authors.initials: Y
authors.lastname: Choi
authors.forename: Hyo Suk
authors.initials: HS
authors.lastname: Nam
authors.forename: Ji Hoe
authors.initials: JH
authors.lastname: Heo
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D034741:RNA, Small Interfering; D037761:Sirtuins; C560607:sirtuin 6, rat; D005947:Glucose; D010100:Oxygen
keywords: 4′,6-diamidino-2-phenylindole; Brain ischemia; DAPI; DMEM; Dulbecco’s Modified Eagle’s Medium; GFAP; H3K9; HMGB1; High mobility group box-1; MCAO; NF-κB; OGD; Oxygen/glucose deprivation; PBS; PI; RECA-1; SIRT; Sir2; Sirtuin 6; glial fibrillary acidic protein; high-mobility group box-1; histone H3 lysine 9; middle cerebral artery occlusion; nuclear factor-κB; oxygen/glucose deprivation; phosphate-buffered saline; propidium iodide; rat endothelial cell antigen-1; silent information regulator 2; sirtuin