In vivo effects of ozone exposure on protein adduct formation by 1-nitronaphthalene in rat lung.
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 vasostatin, was adducted only in ozone-exposed animals. Although vasostatin 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.
Wheelock
Asa M
AM
Department of Molecular Biosciences and Anatomy, School of Veterinary Medicine, University of California, Davis, USA. asa@para-docs.org
Boland
Bridget C
BC
Isbell
Margaret
M
Morin
Dexter
D
Wegesser
Teresa C
TC
Plopper
Charles G
CG
Buckpitt
Alan R
AR
D000393:Air Pollutants / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000378:metabolism* / Q000633:toxicity; D018384:Oxidative Stress; D010126:Ozone / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000393:Air Pollutants; D009281:Naphthalenes; D011506:Proteins; D010126:Ozone; C016614:1-nitronaphthalene