Proteomic Analysis of Secreted Proteins by Human Bronchial Epithelial Cells in Response to Cadmium Toxicity

Proteomics. 2015 Sep;15(17):3075-86. doi: 10.1002/pmic.201400489. Epub 2015 Jun 5.

Abstract

For years, many studies have been conducted to investigate the intracellular response of cells challenged with toxic metal(s), yet, the corresponding secretome responses, especially in human lung cells, are largely unexplored. Here, we provide a secretome analysis of human bronchial epithelial cells (BEAS-2B) treated with cadmium chloride (CdCl2 ), with the aim of identifying secreted proteins in response to Cd toxicity. Proteins from control and spent media were separated by two-dimensional electrophoresis and visualized by silver staining. Differentially-secreted proteins were identified by MALDI-TOF-MS analysis and database searching. We characterized, for the first time, the extracellular proteome changes of BEAS-2B dosed with Cd. Our results unveiled that Cd treatment led to the marked upregulation of molecular chaperones, antioxidant enzymes, enzymes associated with glutathione metabolic process, proteins involved in cellular energy metabolism, as well as tumor-suppressors. Pretreatment of cells with the thiol antioxidant glutathione before Cd treatment effectively abrogated the secretion of these proteins and prevented cell death. Taken together, our results demonstrate that Cd causes oxidative stress-induced cytotoxicity; and the differentially-secreted protein signatures could be considered as targets for potential use as extracellular biomarkers upon Cd exposure.

Keywords: BEAS-2B; Biomedicine; Cadmium; Human lung cells; Mass spectrometry; Secretomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Bronchi / cytology*
  • Bronchi / drug effects
  • Cadmium Chloride / administration & dosage
  • Cadmium Chloride / toxicity*
  • Cell Line / drug effects
  • Cell Line / metabolism
  • Culture Media / analysis
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Glutathione / metabolism
  • Glutathione / pharmacology
  • Humans
  • Oxidative Stress / drug effects
  • Peroxiredoxins / metabolism
  • Proteins / analysis
  • Proteins / metabolism*
  • Proteomics / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antioxidants
  • Culture Media
  • Proteins
  • PRDX1 protein, human
  • Peroxiredoxins
  • Glutathione
  • Cadmium Chloride