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

Xiaoping Ao, David M. Lubman, Mary A. Davis, Xianying Xing, Feng Ming Kong, Theodore S. Lawrence, Ming Zhang

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)417-425
Number of pages9
JournalRadiation Research
Volume169
Issue number4
DOIs
StatePublished - Apr 1 2008

Fingerprint

fibrosis
Proteomics
lungs
mice
Fibrosis
Radiation
proteins
Lung
radiation
inorganic peroxides
Proteins
Alcohol Oxidoreductases
Inbred C57BL Mouse
biliverdin reductase
High Pressure Liquid Chromatography
toxicity
irradiation
Oxidation-Reduction
glycolysis
guanosines

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

Ao, X., Lubman, D. M., Davis, M. A., Xing, X., Kong, F. M., Lawrence, T. S., & Zhang, M. (2008). Comparative proteomic analysis of radiation-induced changes in mouse lung: Fibrosis-sensitive and -resistant strains. Radiation Research, 169(4), 417-425. https://doi.org/10.1667/RR1173.1

Comparative proteomic analysis of radiation-induced changes in mouse lung : Fibrosis-sensitive and -resistant strains. / Ao, Xiaoping; Lubman, David M.; Davis, Mary A.; Xing, Xianying; Kong, Feng Ming; Lawrence, Theodore S.; Zhang, Ming.

In: Radiation Research, Vol. 169, No. 4, 01.04.2008, p. 417-425.

Research output: Contribution to journalArticle

Ao, X, Lubman, DM, Davis, MA, Xing, X, Kong, FM, Lawrence, TS & Zhang, M 2008, 'Comparative proteomic analysis of radiation-induced changes in mouse lung: Fibrosis-sensitive and -resistant strains', Radiation Research, vol. 169, no. 4, pp. 417-425. https://doi.org/10.1667/RR1173.1
Ao, Xiaoping ; Lubman, David M. ; Davis, Mary A. ; Xing, Xianying ; Kong, Feng Ming ; Lawrence, Theodore S. ; Zhang, Ming. / Comparative proteomic analysis of radiation-induced changes in mouse lung : Fibrosis-sensitive and -resistant strains. In: Radiation Research. 2008 ; Vol. 169, No. 4. pp. 417-425.
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