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TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight

文献类型：期刊论文

作者Chen, Qun1,2,4; Wang, Ningning2,4; Zhu, Mingjiang2; Lu, Jianhong2,4; Zhong, Huiqin2,4; Xue, Xinli2,4; Guo, Shuoyuan1,2,4; Li, Min2,4; Wei, Xinben2,4; Tao, Yongzhen2
刊名REDOX BIOLOGY
出版日期2018
卷号15期号:-页码:266-276
ISSN号2213-2317
关键词TiO2 nanoparticles Macrophages Mitochondrial dysfunction Inflammation Proteomics Metabolomics
DOI10.1016/j.redox.2017.12.011
文献子类Article
英文摘要Titanium dioxide nanoparticles (TiO2 NPs) are widely used in food and cosmetics but the health impact of human exposure remains poorly defined. Emerging evidence suggests that TiO2 NPs may elicit immune responses by acting on macrophages. Our proteomic study showed that treatment of macrophages with TiO2 NPs led to significant re-organization of cell membrane and activation of inflammation. These observations were further corroborated with transmission electron microscopy (TEM) experiments, which demonstrated that TiO2 NPs were trapped inside of multi-vesicular bodies (MVB) through endocytotic pathways. TiO2 NP caused significant mitochondrial dysfunction by increasing levels of mitochondrial reactive oxygen species (ROS), decreasing ATP generation, and decreasing metabolic flux in tricarboxylic acid (TCA) cycle from C-13-labelled glutamine using GC-MS-based metabolic flux analysis. Further lipidomic analysis showed that TiO2 NPs significantly decreased levels of cardiolipins, an important class of mitochondria] phospholipids for maintaining proper function of electron transport chains. Furthermore, TiO2 NP exposure activates inflammatory responses by increasing mRNA levels of TNF-alpha, iNOS, and COX-2. Consistently, our targeted metabolomic analysis showed significantly increased production of COX-2 metabolites including PGD(2), PGE(2), and 15d-PGJ(2). In addition, TiO2 NP also caused significant attenuation of phagocytotic function of macrophages. In summary, our studies utilizing multiple powerful omit techniques suggest that human exposure of TiO2 NPs may have profound impact on macrophage function through activating inflammatory responses and causing mitochondrial dysfunction without physical presence in mitochondria.
学科主题Biochemistry & Molecular Biology
WOS关键词TITANIUM-DIOXIDE NANOPARTICLES ; TANDEM MASS-SPECTROMETRY ; LIPID-PEROXIDATION ; OXIDATIVE STRESS ; IN-VIVO ; 4-HYDROXYNONENAL 4-HNE ; IMMUNE TOXICITY ; CARDIOLIPIN ; APOPTOSIS ; EXPOSURE
语种英语
出版者ELSEVIER SCIENCE BV
WOS记录号WOS:000436226600025
版本出版稿
源URL[http://202.127.25.144/handle/331004/735]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China;
2.Chinese Acad Sci, SIBS, INS, Key Lab Food Safety Res, Shanghai, Peoples R China;
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China,
4.Univ Chinese Acad Sci, CAS, Beijing, Peoples R China;
推荐引用方式
GB/T 7714		 Chen, Qun,Wang, Ningning,Zhu, Mingjiang,et al. TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight[J]. REDOX BIOLOGY,2018,15(-):266-276.
APA Chen, Qun.,Wang, Ningning.,Zhu, Mingjiang.,Lu, Jianhong.,Zhong, Huiqin.,...&,.(2018).TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight.REDOX BIOLOGY,15(-),266-276.
MLA Chen, Qun,et al."TiO2 nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight".REDOX BIOLOGY 15.-(2018):266-276.

入库方式： OAI收割

来源：上海营养与健康研究所

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