Time-dependent response of A549 cells upon exposure to cadmium

J Appl Toxicol. 2018 Nov;38(11):1437-1446. doi: 10.1002/jat.3665. Epub 2018 Jul 26.

Abstract

Cadmium is considered one of the most harmful carcinogenic heavy metals in the human body. Although many scientists have performed research on cadmium toxicity mechanism, the toxicokinetic process of cadmium toxicity remains unclear. In the present study, the kinetic response of proteome in/and A549 cells to exposure of exogenous cadmium was profiled. A549 cells were treated with cadmium sulfate (CdSO4 ) for different periods and expressions of proteins in cells were detected by two-dimensional gel electrophoresis. The kinetic expressions of proteins related to cadmium toxicity were further investigated by reverse transcription-polymerase chain reaction and western blotting. Intracellular cadmium accumulation and content fluctuation of several essential metals were observed after 0-24 hours of exposure by inductively coupled plasma mass spectrometry. Fifty-four protein spots showed significantly differential responses to CdSO4 exposure at both 4.5 and 24 hours. From these proteins, four expression patterns were concluded. Their expressions always exhibited a maximum abundance ratio after CdSO4 exposure for 24 hours. The expression of metallothionein-1 and ZIP-8, concentration of total protein, and contents of cadmium, zinc, copper, cobalt and manganese in cells also showed regular change. In synthesis, the replacement of the essential metals, the inhibition of the expression of metal storing protein and the activation of metal efflux system are involved in cadmium toxicity.

Keywords: cadmium; kinetic processes; metal homeostasis; protein expression; time-dependent change.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cadmium / metabolism
  • Cadmium / toxicity*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Humans
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Proteome / genetics
  • Proteome / metabolism*
  • Time Factors
  • Toxicokinetics

Substances

  • Cation Transport Proteins
  • Proteome
  • SLC39A8 protein, human
  • Cadmium
  • Metallothionein