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Comparative Study
. 2016 Jan 1:130:85-93.
doi: 10.1016/j.jprot.2015.09.010. Epub 2015 Sep 14.

Comparative plasma proteomic studies of pulmonary TiO2 nanoparticle exposure in rats using liquid chromatography tandem mass spectrometry

Megan M Maurer  1 , Gregory C Donohoe  1 , Hossein Maleki  1 , Jinghai Yi  2 , Carroll McBride  2 , Timothy R Nurkiewicz  2 , Stephen J Valentine  3
Affiliations
Comparative Study

Comparative plasma proteomic studies of pulmonary TiO2 nanoparticle exposure in rats using liquid chromatography tandem mass spectrometry

Megan M Maurer et al. J Proteomics. .

Abstract

Mounting evidence suggests that pulmonary exposure to nanoparticles (NPs) has a toxic effect on biological systems. A number of studies have shown that exposure to NPs result in systemic inflammatory response, oxidative stress, and leukocyte adhesion. However, significant knowledge gaps exist for understanding the key molecular mechanisms responsible for altered microvasculature function. Utilizing comprehensive LC-MS/MS and comparative proteomic analysis strategies, important proteins related to TiO2 NP exposure in rat plasma have been identified. Molecular pathway analysis of these proteins revealed 13 canonical pathways as being significant (p ≤ 0.05), but none were found to be significantly up or down-regulated (z>|2|). This work lays the foundation for future research that will monitor relative changes in protein abundance in plasma and tissue as a function of post-exposure time and TiO2 NP dosage to further elucidate mechanisms of pathway activation as well as to decipher other affected pathways.

Keywords: Biopathway analysis; Proteomics; TiO(2) nanoparticles.

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Figures

Figure 1
Figure 1
A. The top 19 protein locations, totaling 500 hits, along with the counts for all indentified proteins in control and exposed samples. B. The top 18 protein functions totaling 308 hits for all identified proteins in control and exposed samples.
Figure 2
Figure 2
PCA scatter plot, generated in JMP, is derived from the emPAI scores of the 58 proteins identified by at least 2 unique peptides and found in 3 or more samples. Control samples are shown in red and exposed samples are shown in blue. Sample regions are shown as semi-transparent shading of the correlating color.
Figure 3
Figure 3
Network 1 from IPA showing the inter-relationships between relevant proteins. Solid lines indicate direct relationships and dashed lines indicate indirect relationships. Loops represent feedback systems. The inter-relationships shown are known from the IPA database. The 38 input molecules are highlighted in green (increased in abundance) and red (decreased in abundance). The network hubs are Prothrombin (F2) and Interleukin-1 (IL1).
Figure 4
Figure 4
IPA canonical pathways generated from input molecules. The bars indicate the p-value of the pathway; blue bars indicate a negative z-score (down regulation of the pathway) and orange bars indicate a positive z-score (up regulation of the pathway). The orange boxes indicate the ratio of the number of input molecules to total number of molecules in the pathway.
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