In vivo effects of ozone exposure on protein adduct formation by 1-nitronaphthalene in rat lung

Åsa M. Wheelock, Bridget C. Boland, Margaret Isbell, Dexter Morin, Teresa C. Wegesser, Charles Plopper, Alan R Buckpitt

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The incidence of serious photochemical smog events is steadily growing in urban environments around the world. The electrophilic metabolites of 1-nitronaphthalene (1-NN), a common air pollutant in urban areas, have been shown to bind covalently to proteins. 1-NN specifically targets the airway epithelium, and the toxicity is synergized by prior long-term ozone exposure in rat. In this study we investigated the formation of 1-NN protein adducts in the rat airway epithelium in vivo and examined how prior long-term ozone exposure affects adduct formation. Eight adducted proteins, several involved in cellular antioxidant defense, were identified. The extent of adduction of each protein was calculated, and two proteins, peroxiredoxin 6 and biliverdin reductase, were adducted at high specific activities (0.36-0.70 and 1.0 nmol adduct/nmol protein). Furthermore, the N-terminal region of calreticulin, known as vaso-statin, was adducted only in ozone-exposed animals. Although vaso-statin was adducted at relatively low specific activity (0.01 nmol adduct/nmol protein), the adduction only in ozone-exposed animals makes it a candidate protein for elucidating the synergistic toxicity between ozone and 1-NN. These studies identified in vivo protein targets for reactive 1-NN metabolites that are potentially associated with the mechanism of 1-NN toxicity and the synergistic effects of ozone.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume33
Issue number2
DOIs
StatePublished - Aug 2005

Keywords

  • 1-nitronaphthalene
  • Calreticulin
  • Ozone
  • Protein adduct
  • Proteomics

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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