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 language | English (US) |
|---|---|
| Pages (from-to) | 130-137 |
| Number of pages | 8 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 33 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2005 |
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Keywords
- 1-nitronaphthalene
- Calreticulin
- Ozone
- Protein adduct
- Proteomics
ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
Cite this
In vivo effects of ozone exposure on protein adduct formation by 1-nitronaphthalene in rat lung. / Wheelock, Åsa M.; Boland, Bridget C.; Isbell, Margaret; Morin, Dexter; Wegesser, Teresa C.; Plopper, Charles; Buckpitt, Alan R.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 33, No. 2, 08.2005, p. 130-137.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vivo effects of ozone exposure on protein adduct formation by 1-nitronaphthalene in rat lung
AU - Wheelock, Åsa M.
AU - Boland, Bridget C.
AU - Isbell, Margaret
AU - Morin, Dexter
AU - Wegesser, Teresa C.
AU - Plopper, Charles
AU - Buckpitt, Alan R
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
KW - 1-nitronaphthalene
KW - Calreticulin
KW - Ozone
KW - Protein adduct
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=22944470463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22944470463&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2005-0047OC
DO - 10.1165/rcmb.2005-0047OC
M3 - Article
C2 - 15845863
AN - SCOPUS:22944470463
VL - 33
SP - 130
EP - 137
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 2
ER -