Sirt3-MnSOD axis represses nicotine-induced mitochondrial oxidative stress and mtDNA damage in osteoblasts

• Published in: Acta biochimica et biophysica Sinica 2015-04, Vol.47 (4), p.306-312
• Main Authors: Li, Yong, Yu, Chen, Shen, Guangsi, Li, Guangfei, Shen, Junkang, Xu, Youjia, Gong, Jianping
• Format: Article
• Language: English
• Subjects: Acetylation - drug effects; Animals; Blotting, Western; Cells, Cultured; DNA Damage; DNA, Mitochondrial - genetics; Down-Regulation - drug effects; Ganglionic Stimulants - toxicity; Humans; Metalloporphyrins - pharmacology; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; MnSOD; Nicotine - toxicity; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Oxidative Stress - drug effects; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sirtuin 3 - genetics; Sirtuin 3 - metabolism; Superoxide Dismutase - metabolism; 尼古丁; 成骨细胞分化; 损伤; 氧化应激; 线粒体DNA; 诱导; 锰超氧化物歧化酶
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmv013

Increasing evidence has suggested an important role played by reactive oxygen species in the patho- genesis of osteoporosis. Tobacco smoking is an important risk factor for the development of osteo- porosis, 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 dif- ferentiated 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. More- over, 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 re- duce the effect of nicotine on osteoblasts. In summary, Sirt3-MnSOD axis was identified as a nega- tive component in nicotine-induced rnitochondrial oxidative stress and mtDNA damage, and MnTBAP may serve as a potential therapeutic drug for osteoporosis.