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

ABSTRACT: 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 ¹³C-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 mitochondrial phospholipids for maintaining proper function of electron transport chains. Furthermore, TiO₂ NP exposure activates inflammatory responses by increasing mRNA levels of TNF-α, iNOS, and COX-2. Consistently, our targeted metabolomic analysis showed significantly increased production of COX-2 metabolites including PGD₂, PGE₂, and 15d-PGJ₂. In addition, TiO₂ NP also caused significant attenuation of phagocytotic function of macrophages. In summary, our studies utilizing multiple powerful omic 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.

SUBMITTER: Chen Q

PROVIDER: S-EPMC5752088 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Chen Qun Q Wang Ningning N Zhu Mingjiang M Lu Jianhong J Zhong Huiqin H Xue Xinli X Guo Shuoyuan S Li Min M Wei Xinben X Tao Yongzhen Y Yin Huiyong H

Redox biology 20171228

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 m ...[more]

PMID: 29294438

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Project description:A series of facet-engineered TiO2/BaFe12O19 composites were synthesized through hydrothermal growth of both phases and subsequent deposition of the different, faceted TiO2 nanoparticles onto BaFe12O19 microplates. The well-defined geometry of the composite and uniaxial magnetic anisotropy of the ferrite allowed alternate interfaces between both phases and fixed the orientation between the TiO2 crystal structure and the remanent magnetic field within BaFe12O19. The morphology and crystal structure of the composites were confirmed by a combination of scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses together with the detailed study of BaFe12O19 electronic and magnetic properties. The photocatalytic activity and magnetic field effect were studied in the reaction of phenol degradation for TiO2/BaFe12O19 and composites of BaFe12O19 covered with a SiO2 protective layer and TiO2. The observed differences in phenol degradation are associated with electron transfer and the contribution of the magnetic field. All obtained magnetic composite materials can be easily separated in an external magnetic field, with efficiencies exceeding 95%, and recycled without significant loss of photocatalytic activity. The highest activity was observed for the composite of BaFe12O19 with TiO2 exposing {1 0 1} facets. However, to prevent electron transfer within the composite structure, this photocatalyst material was additionally coated with a protective SiO2 layer. Furthermore, TiO2 exposing {1 0 0} facets exhibited significant synergy with the BaFe12O19 magnetic field, leading to 2 times higher photocatalytic activity when ferrite was magnetized before the process. The photoluminescence emission study suggests that for this particular combination, the built-in magnetic field of the ferrite suppressed the recombination of the photogenerated charge carriers. Ultimately, possible effects of complex electro/magnetic interactions within the magnetic photocatalyst are shown and discussed for the first time, including the anisotropic properties of both phases.

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

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TiO<sub>2</sub> nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight.

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