Comparative proteomic analysis of radiation-induced changes in mouse lung: fibrosis-sensitive and -resistant strains

Radiat Res. 2008 Apr;169(4):417-25. doi: 10.1667/RR1173.1.

Abstract

To determine whether comparative proteomics could detect differential protein expression after lung irradiation in two mouse strains with different radiation responses, lung proteins were subjected to two-dimensional orthogonal liquid-phase separations, with chromatofocusing in the first dimension and nonporous silica reverse-phase high-performance liquid chromatography (NPS-RP-HPLC) in the second. Five weeks after 12 Gy whole-lung irradiation, 15 and 31 proteins had significantly altered expression levels in C3H/HeJ (less likely to develop lung fibrosis) and C57BL/6J mice (more likely to develop lung fibrosis), respectively. These proteins were analyzed by HPLC-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and identified by matching sequences in a peptide database. The proteins are associated with redox, energy consumption, glycolysis, or chromatin/ RNA structure formation. Five of the six redox-related proteins, including superoxide dismutase 1 (SOD1), cytochrome c oxidase, glutamate dehydrogenase, biliverdin reductase, peroxiredoxin and carbonyl reductase, were down-regulated in the irradiated C57BL/6J mice, whereas SOD1, sulfurtransferase and carbonyl reductase increased in the irradiated C3H/ HeJ mice. Thus decreased antioxidant proteins in the irradiated C57BL/6J mice may be correlated with increased early lung toxicity. Changes in SOD1 and 8-hydroxydeoxy-guanosine (8-OHdG, an oxidative stress marker) were further confirmed by immunohistochemistry and/or Western blot analysis. These data suggest that a proteomics approach has the potential to detect protein changes relevant to early lung toxicity after irradiation.

Publication types

  • Comparative Study

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Lung / chemistry
  • Lung / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Proteomics*
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / metabolism*
  • Radiation Tolerance
  • Superoxide Dismutase / analysis
  • Superoxide Dismutase-1

Substances

  • 8-Hydroxy-2'-Deoxyguanosine
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Deoxyguanosine