title: SIRT2 is required for lipopolysaccharide-induced activation of BV2 microglia.
abstract: It has been reported that inhibition of sirtuin 2 (SIRT2), a sirtuin family protein, can decrease cellular and tissue injuries in models of Parkinson's disease (PD) and Huntington's disease (HD); however, the mechanisms underlying these observations have remained unclear. Because inflammation plays key pathological roles in multiple major neurological disorders including PD and HD, in our current study we tested our hypothesis that SIRT2 plays an important role in microglial activation. We found that treatment of BV2 microglia with lipopolysaccharides led to significant increases in NO and inducible nitric oxide synthase mRNA levels, as well as increases in the levels of tumor necrosis factor-α and interleukin 6 mRNA, which indicated microglial activation. These increases were significantly decreased in the cells with SIRT2 silencing-produced decreases in the SIRT2 level. These observations suggest that SIRT2 is required for lipopolysaccharide-induced microglial activation. The findings also suggest that SIRT2 may be a therapeutic target for inhibiting the inflammatory responses in neurological disorders such as PD and HD.
authors.affiliation: aMed-X Research Institute, School of Biomedical Engineering bDepartment of Neurology, Ruijin Hospital cDepartment of Neurology, Third People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Heyu
authors.initials: H
authors.lastname: Chen
authors.forename: Danhong
authors.initials: D
authors.lastname: Wu
authors.forename: Xianting
authors.initials: X
authors.lastname: Ding
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2