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Single-wall carbon nanohorns inhibited activation of microglia induced by lipopolysaccharide through blocking of Sirt3

Lihong Li1, Jinqian Zhang2, Yang Yang1, Qiang Wang1, Li Gao1, Yanlong Yang1, Tao Chang1, Xingye Zhang1, Guoan Xiang3, Yongmei Cao4, Zujin Shi5, Ming Zhao6 and Guodong Gao1*

Author affiliations

1 Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, 710038, Xi’an, China

2 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 100015, Beijing, China

3 Department of General Surgery, the Second People’s Hospital of Guangdong Province, 510515, Guangzhou, China

4 International Mongolian Medical Hospital of Inner Mongolia, 010065, Hohhot, China

5 Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, 100871, Beijing, China

6 Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, 100191, Beijing, China

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Citation and License

Nanoscale Research Letters 2013, 8:100  doi:10.1186/1556-276X-8-100

Published: 22 February 2013

Abstract

Single-wall carbon nanohorns (SWNHs) have been demonstrated to accumulate in cytotoxic levels within organs of various animal models and cell types, which emerge as a wide range of promising biomedical imaging. Septic encephalopathy (SE) is an early sign of sepsis and associated with an increased rate of morbidity and mortality. Microglia activation plays an important role in neuroinflammation, which contributes to neuronal damage. Inhibition of microglia activation may have therapeutic benefits, which can alleviate the progression of neurodegeneration. Therefore, we investigated the functional changes of mice microglia cell lines pre-treated with or without lipopolysaccharide (LPS) induced by SWNHs. To address this question, the research about direct role of SWNHs on the growth, proliferation, and apoptosis of microglia cell lines in mice (N9 and BV2) pre-treated with or without LPS had been performed. Our results indicate that the particle diameter of SWNHs in water is between 342 to 712 nm. The images in scanning electron microscope showed that SWNHs on polystyrene surface are individual particles. LPS induced activation of mice microglia, promoted its growth and proliferation, and inhibited its apoptosis. SWNHs inhibited proliferation, delayed mitotic entry, and promoted apoptosis of mice microglia cells. The effects followed gradually increasing cultured time and concentrations of SWNHs, especially in cells pre-treated with LPS. SWNHs induced a significantly increase in G1 phase and inhibition of S phase of mice microglia cells in a dose-manner dependent of SWNHs, especially in cells pre-treated with LPS. The transmission electron microscope images showed that individual spherical SWNH particles smaller than 100 nm in diameters were localized inside lysosomes of mice microglia cells. SWNHs inhibited mitotic entry, growth and proliferation of mice microglia cells, and promoted its apoptosis, especially in cells pre-treated with LPS. SWNHs inhibited expression of Sirt3 and energy metabolism related with Sirt3 in mice microglia cells in a dose-dependent manner, especially in cells pre-treated with LPS. The role of SWNHs on mice microglia was implicating Sirt3 and energy metabolism associated with it.

Keywords:
Single-walled carbon nanohorns; Septic encephalopathy; Cell proliferation; Apoptosis; Lipopolysaccharide; Sepsis; Sirt3