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Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study.

Pan CH, Chuang KJ, Chen JK, Hsiao TC, Lai CH, Jones TP, BéruBé KA, Hong GB, Ho KF, Chuang HC - Int J Nanomedicine (2015)

Bottom Line: An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways.A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein.Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times.

View Article: PubMed Central - PubMed

Affiliation: Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, Taiwan ; School of Public Health, National Defense Medical Center, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP.

No MeSH data available.


Related in: MedlinePlus

The pathways associated with the downregulation and upregulation of the protein responses 24 hours after exposure to ZnONP.Notes: The pathways were determined using DAVID analysis. An enhanced score (−log[P-value]) ≥1.3 threshold (red line) was considered to be significant.Abbreviations: ZnONP, zinc oxide nanoparticle; TCA, tricarboxylic acid; DAVID, Database for Annotation, Visualization and Integrated Discover.
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f5-ijn-10-4705: The pathways associated with the downregulation and upregulation of the protein responses 24 hours after exposure to ZnONP.Notes: The pathways were determined using DAVID analysis. An enhanced score (−log[P-value]) ≥1.3 threshold (red line) was considered to be significant.Abbreviations: ZnONP, zinc oxide nanoparticle; TCA, tricarboxylic acid; DAVID, Database for Annotation, Visualization and Integrated Discover.

Mentions: Downregulated proteins involved in 24 pathways were identified in the 24-hour group, and 18 of these pathways were considered to be significant (Figure 5). These included glycolysis/gluconeogenesis, citrate cycle (TCA cycle), glutathione metabolism, pyruvate metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism, propanoate metabolism, glyoxylate and dicarboxylate metabolism, tryptophan metabolism, leukocyte transendothelial migration, fatty acid elongation in the mitochondria, regulation of the actin cytoskeleton, fatty acid metabolism, pentose phosphate pathway, neurotrophin signaling pathway, fructose and mannose metabolism, cell cycle, and focal adhesion. The upregulated proteins in the 24-hour data set implicated eleven pathways, six of which were considered to be significant and are involved in antigen processing and presentation, tight junctions, MAPK pathway, endocytosis, adherens junctions, and ribosome. In the 28-day group (Figure 6), eight downregulated pathways were identified, with significance being observed for six. These included glycolysis/gluconeogenesis, pentose phosphate pathway, hypertrophic cardiomyopathy (HCM), antigen processing and presentation, fructose and mannose metabolism, and pyruvate metabolism. Regarding the upregulation in the 28-day group, cell cycle, neurotrophin signaling pathway, oocyte meiosis, glutathione metabolism, and metabolism of xenobiotics by cytochrome P450 were identified as significant. In a comparison between the significant pathways for the 24- and 28-day groups, we observed that the downregulated pathways for both the time frames considered included glycolysis/gluconeogenesis, pentose phosphate pathway, fructose and mannose metabolism, and pyruvate metabolism, whereas antigen processing and presentation which was upregulated in the 24-hour group became downregulated in the 28-day group. Furthermore, cell cycle, neurotrophin signaling pathway, glutathione metabolism, and metabolism of xenobiotics by cytochrome P450 which were downregulated in the 24-hour group were upregulated in the 28-day group.


Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study.

Pan CH, Chuang KJ, Chen JK, Hsiao TC, Lai CH, Jones TP, BéruBé KA, Hong GB, Ho KF, Chuang HC - Int J Nanomedicine (2015)

The pathways associated with the downregulation and upregulation of the protein responses 24 hours after exposure to ZnONP.Notes: The pathways were determined using DAVID analysis. An enhanced score (−log[P-value]) ≥1.3 threshold (red line) was considered to be significant.Abbreviations: ZnONP, zinc oxide nanoparticle; TCA, tricarboxylic acid; DAVID, Database for Annotation, Visualization and Integrated Discover.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524458&req=5

f5-ijn-10-4705: The pathways associated with the downregulation and upregulation of the protein responses 24 hours after exposure to ZnONP.Notes: The pathways were determined using DAVID analysis. An enhanced score (−log[P-value]) ≥1.3 threshold (red line) was considered to be significant.Abbreviations: ZnONP, zinc oxide nanoparticle; TCA, tricarboxylic acid; DAVID, Database for Annotation, Visualization and Integrated Discover.
Mentions: Downregulated proteins involved in 24 pathways were identified in the 24-hour group, and 18 of these pathways were considered to be significant (Figure 5). These included glycolysis/gluconeogenesis, citrate cycle (TCA cycle), glutathione metabolism, pyruvate metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism, propanoate metabolism, glyoxylate and dicarboxylate metabolism, tryptophan metabolism, leukocyte transendothelial migration, fatty acid elongation in the mitochondria, regulation of the actin cytoskeleton, fatty acid metabolism, pentose phosphate pathway, neurotrophin signaling pathway, fructose and mannose metabolism, cell cycle, and focal adhesion. The upregulated proteins in the 24-hour data set implicated eleven pathways, six of which were considered to be significant and are involved in antigen processing and presentation, tight junctions, MAPK pathway, endocytosis, adherens junctions, and ribosome. In the 28-day group (Figure 6), eight downregulated pathways were identified, with significance being observed for six. These included glycolysis/gluconeogenesis, pentose phosphate pathway, hypertrophic cardiomyopathy (HCM), antigen processing and presentation, fructose and mannose metabolism, and pyruvate metabolism. Regarding the upregulation in the 28-day group, cell cycle, neurotrophin signaling pathway, oocyte meiosis, glutathione metabolism, and metabolism of xenobiotics by cytochrome P450 were identified as significant. In a comparison between the significant pathways for the 24- and 28-day groups, we observed that the downregulated pathways for both the time frames considered included glycolysis/gluconeogenesis, pentose phosphate pathway, fructose and mannose metabolism, and pyruvate metabolism, whereas antigen processing and presentation which was upregulated in the 24-hour group became downregulated in the 28-day group. Furthermore, cell cycle, neurotrophin signaling pathway, glutathione metabolism, and metabolism of xenobiotics by cytochrome P450 which were downregulated in the 24-hour group were upregulated in the 28-day group.

Bottom Line: An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways.A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein.Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times.

View Article: PubMed Central - PubMed

Affiliation: Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, Taiwan ; School of Public Health, National Defense Medical Center, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP.

No MeSH data available.


Related in: MedlinePlus