Molecular Control of TiO2-NPs Toxicity Formation at Predicted Environmental Relevant Concentrations by Mn-SODs Proteins

Abstract

With growing concerns of the safety of nanotechnology, the in vivo toxicity of nanoparticles (NPs) at environmental relevant concentrations has drawn increasing attentions. We investigated the possible molecular mechanisms of titanium nanoparticles (Ti-NPs) in the induction of toxicity at predicted environmental relevant concentrations. In nematodes, small sizes (4 nm and 10 nm) of TiO2-NPs induced more severe toxicities than large sizes (60 nm and 90 nm) of TiO2-NPs on animals using lethality, growth, reproduction, locomotion behavior, intestinal autofluorescence, and reactive oxygen species (ROS) production as endpoints. Locomotion behaviors could be significantly decreased by exposure to 4-nm and 10-nm TiO2-NPs at concentration of 1 ng/L in nematodes. Among genes required for the control of oxidative stress, only the expression patterns of sod-2 and sod-3 genes encoding Mn-SODs in animals exposed to small sizes of TiO2-NPs were significantly different from those in animals exposed to large sizes of TiO2-NPs. sod-2 and sod-3 gene expressions were closely correlated with lethality, growth, reproduction, locomotion behavior, intestinal autofluorescence, and ROS production in TiO2-NPs-exposed animals. Ectopically expression of human and nematode Mn-SODs genes effectively prevented the induction of ROS production and the development of toxicity of TiO2-NPs. Therefore, the altered expression patterns of Mn-SODs may explain the toxicity formation for different sizes of TiO2-NPs at predicted environmental relevant concentrations. In addition, we demonstrated here a strategy to investigate the toxicological effects of exposure to NPs upon humans by generating transgenic strains in nematodes for specific human genes.

Combination of bioanalytical approaches and quantitative proteomics for the elucidation of the toxicity mechanisms associated to TiO2 nanoparticles exposure in human keratinocytes

“…That is the case of SOD2, a mitochondrial protein involved in the conversion of O 2to H2O2, which was found was found inhibited (RSILAC = -2.71); thus confirming a potential imbalance of ROS in keratinocytes exposed to TiO2-NPs. This result is in agreement with the observations carried out by Li et al in TiO2-NPs exposed nematodes (Li et al 2012). Additionally, when cells undergo increased ROS levels and oxidative stress, there are certain proteins that act as a defense mechanism and whose overexpression may be used as an oxidative stress marker.…”

Excessive production of mitochondrion‑derived reactive oxygen species induced by titanium ions leads to autophagic cell death of osteoblasts via the SIRT3/SOD2 pathway

“…The amount of SOD2 protein is regulated by transcription, and its activity is regulated by acetylation level (23,24,50). Consistent with previous studies (53,54), Ti ion exposure in the present study resulted in an elevated level of acetylation of SOD2 in a dose-dependent manner. Therefore, the present results suggested that Ti ions increased mitochondrial oxygen free radicals by increasing SOD2 acetylation levels, rather than by decreasing SOD2 protein expression levels.…”

Toxicity evaluation of boron nitride nanospheres and water-soluble boron nitride in <em>Caenorhabditis elegans</em>

“…14 As a sensitive and cost-efficient wholeanimal model with a short life cycle, C. elegans complements mammalian models [15][16][17][18] for assessing the toxicity of NMs at the organism or population level. [19][20][21] These NMs include metal nanoparticles (NPs; TiO 2 , Al 2 O 3 , and ZnO 2 ) [22][23][24] and carbon NPs (carbon NTs [CNTs], graphene oxide [GO], and graphite nanoplatelets). [25][26][27][28] Here, we analyze the two aforementioned representative forms of BN NMs in C. elegans: BNNSs and BN-800-2.…”