title: Sirt3-MnSOD axis represses nicotine-induced mitochondrial oxidative stress and mtDNA damage in osteoblasts.
abstract: Increasing evidence has suggested an important role played by reactive oxygen species in the pathogenesis of osteoporosis. Tobacco smoking is an important risk factor for the development of osteoporosis, and nicotine is one of the major components in tobacco. However, the mechanism by which nicotine promotes osteoporosis is not fully understood. Here, in this study, we found that nicotine-induced mitochondrial oxidative stress and mitochondrial DNA (mtDNA) damage in osteoblasts differentiated from mouse mesenchymal stem cell. The activity of MnSOD, one of the mitochondrial anti-oxidative enzymes, was significantly reduced by nicotine due to the reduced level of Sirt3. Moreover, it was also found that Sirt3 could promote MnSOD activity by deacetylating MnSOD. Finally, Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP, a MnSOD mimetic) was found to markedly reduce the effect of nicotine on osteoblasts. In summary, Sirt3-MnSOD axis was identified as a negative component in nicotine-induced mitochondrial oxidative stress and mtDNA damage, and MnTBAP may serve as a potential therapeutic drug for osteoporosis.
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Guangsi
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Guangfei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Junkang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China unionlab@yeah.net jianping_gonggong@126.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005731:Ganglionic Stimulants / Q000633:toxicity; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D005731:Ganglionic Stimulants; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; C525046:Sirt3 protein, mouse; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D009538:Nicotine; D013482:Superoxide Dismutase; D056566:Sirtuin 3
keywords: MnSOD; Sirt3; mitochondrial oxidative stress; mtDNA damage; nicotine; osteoblasts