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Proteomics identification for toxicological pathways screening: A partial difference between low concentration ionic and nanoparticulate silver

ABSTRACT: LC-MS/MS based proteomics coupled with online bioinformatics platform was under evaluation for the better understanding of toxicological pathways induced by silver nanoparticle (AgNP), and to distinguish the difference of such pathways induced by ionic silver. This approach was appraised using AgNP as a model to develop a platform technology for toxicological screening of nanoparticles (NPs), which is currently incorporated into various consumer products. Proteomic study was conducted by exposing human carcinoma cell line to AgNP or AgNO3 for 48 hours at low cytotoxic concentration (LC10). The comparison of proteins expressed in each treatment group was performed using One-way ANOVA (p < 0.05). Proteins with more than 4-fold differentially-expressed were subjected to functional pathway analysis by STITCH. Principal component analysis (PCA) showed the significant variation of proteins identified in each treatment group. Most identified proteins were functioned in cellular process. SOTA clustering indicated the similarity of protein expression between AgNP and control group. We established the resemblance of proteins in cell cycle pathway affected by both Ag substances. While the difference in toxicological pathways from AgNO3 were involved in cellular organization and regulation of metabolic process of macromolecule, and nucleic acid metabolic process were altered by AgNP. The present study supported the practicability of LC-MS/MS based proteomics coupled with STITCH bioinformatics platform, for the identification of toxicological pathways from ionic and AgNP, which were discovered to be partially different. We appraised this platform technology to be promising and powerful for toxicological screening of other new substances.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epidermal Cell, Cell Culture

DISEASE(S): Skin Cancer

SUBMITTER: Pawitrabhorn Samutrtai

LAB HEAD: Pawitrabhorn Samutrtai

PROVIDER: PXD012793 | Pride | 2020-08-18

REPOSITORIES: pride

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			Action	DRS
	200219_mzid.DerivedFromSearch26d279f4-90d9-4ada-9bc8-5aeaa6ec223a.mgf	Mgf
	200219_mzid.DerivedFromSearch26d279f4-90d9-4ada-9bc8-5aeaa6ec223a.pride.mgf.gz	Mgf
	200219_mzid.DerivedFromSearch578c1f51-a33a-4718-8ee5-d2f8b02dbcb1.mgf	Mgf
	200219_mzid.DerivedFromSearch578c1f51-a33a-4718-8ee5-d2f8b02dbcb1.pride.mgf.gz	Mgf
	200219_mzid.mzid.gz	Mzid

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Project description:Nanowires (NWs), high-aspect-ratio nanomaterials, are increasingly used in technological materials and consumer products and may have toxicological characteristics distinct from nanoparticles. We carried out a comprehensive evaluation of the physicochemical stability of four silver nanowires (AgNWs) of two sizes and coatings and their toxicity to Daphnia magna. Inorganic aluminum-doped silica coatings were less effective than organic poly(vinyl pyrrolidone) coatings at preventing silver oxidation or Ag+ release and underwent a significant morphological transformation within 1 h following addition to low ionic strength Daphnia growth media. All AgNWs were highly toxic to D. magna but less toxic than ionic silver. Toxicity varied as a function of AgNW dimension, coating, and solution chemistry. Ag+ release in the media could not account for observed AgNW toxicity. Single-particle inductively coupled plasma mass spectrometry distinguished and quantified dissolved and nanoparticulate silver in microliter-scale volumes of Daphnia magna hemolymph with a limit of detection of approximately 10 ppb. The silver levels within the hemolymph of Daphnia exposed to both Ag+ and AgNW met or exceeded the initial concentration in the growth medium, indicating effective accumulation during filter feeding. Silver-rich particles were the predominant form of silver in hemolymph following exposure to both AgNWs and Ag+. Scanning electron microscopy imaging of dried hemolymph found both AgNWs and silver precipitates that were not present in the AgNW stock or the growth medium. Both organic and inorganic coatings on the AgNW were transformed during ingestion or absorption. Pathway, gene ontology, and clustering analyses of gene expression response indicated effects of AgNWs distinct from ionic silver on Daphnia magna. Four replicates each of five toxicant exposure groups of ~20 animals and four replicates of control, unexposed animals. Each control was compared to each exposed data set for a total of 16 comparisons per chemical condition.

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Proteomics identification for toxicological pathways screening: A partial difference between low concentration ionic and nanoparticulate silver

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