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

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.

Keywords:

• glycolysis
• iTRAQ
• metabolism
• nanoparticles
• S100-A9

Acknowledgments

The authors thank Miss Yi-Syuan Lin, His-En Hua, and Yen-Ling Shen for technical assistance during this project. The authors are grateful of technical support from Animal Molecular Imaging Core Facility at Taiwan National Health Research Institutes (NM-103-PP-04) and for intelligent input from Mr Wei-Neng Liao (NM-103-PP-07). This study was funded by the Institute of Occupational Safety and Health, Taiwan Council of Labor Affairs (IOSH102-M321 and IOSH103-M312).

Author contributions

All authors have contributed substantially to the concept, design, drafting the article, and critical revision of the paper for important intellectual content. All authors read and approved the final version of the paper for publication.

Disclosure

The authors report no conflicts of interest in this work.