Cytochrome P450 2E1 in rat tracheobronchial airways: Response to ozone exposure

Katherine C. Watt, Charles Plopper, Alison J. Weir, Brian Tarkington, Alan R Buckpitt

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The distal trachea and centriacinus of the lung are primary sites of acute injury during short-term ozone exposure; long-term exposure yields cells in these areas that are resistant to high doses of oxidant gases. Epithelial cells located in primary sites for ozone injury are also targets for chemicals that undergo cytochrome P450 (CYP)-dependent activation. These studies were designed to compare the effects of ozone exposure on pulmonary CYP2E1 in susceptible and nonsusceptible sites within the airway tree of lung. CYP2E1 activity was measured in well-defined regions of airways using p-nitrophenol, a CYP2E1-selective substrate, with HPLC/electrochemical detection of the p-nitrocatechol. Alterations in distribution of CYP2E1 were evaluated by immunohistochemistry. CYP2E1 activities were highest in the distal bronchioles and minor daughter airways but were much lower in the lobar bronchi/major daughter airways and trachea. Immediately after short- term ozone exposures (8 h, 1 ppm), CYP2E1 activities were elevated only in the lobar bronchi/major daughter airways. These activities remained above the filtered air control at 1 day but returned to control levels by 2 days. Immunohistochemical assessment of CYP2E1 protein in ozone and filtered air- exposed animals was consistent with the activity measurements. After long- term ozone exposures (90 days, 1 ppm), CYP2E1 activities were decreased in the major and minor daughter airways. These studies indicate that CYP2E1 activities vary substantially by airway level. However, ozone exposure only results in minimal alterations in activity with varying concentration of ozone, length of exposure, and time after exposure in any of the lung subcompartments examined.

Original languageEnglish (US)
Pages (from-to)195-202
Number of pages8
JournalToxicology and Applied Pharmacology
Volume149
Issue number2
DOIs
StatePublished - Apr 1998

Fingerprint

Cytochrome P-450 CYP2E1
Ozone
Rats
Lung
Bronchi
Trachea
Air
Bronchioles
Level control
Wounds and Injuries
Oxidants
Cytochrome P-450 Enzyme System
Animals
Gases
Epithelial Cells
Chemical activation
Immunohistochemistry
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Cytochrome P450 2E1 in rat tracheobronchial airways : Response to ozone exposure. / Watt, Katherine C.; Plopper, Charles; Weir, Alison J.; Tarkington, Brian; Buckpitt, Alan R.

In: Toxicology and Applied Pharmacology, Vol. 149, No. 2, 04.1998, p. 195-202.

Research output: Contribution to journalArticle

Watt, Katherine C. ; Plopper, Charles ; Weir, Alison J. ; Tarkington, Brian ; Buckpitt, Alan R. / Cytochrome P450 2E1 in rat tracheobronchial airways : Response to ozone exposure. In: Toxicology and Applied Pharmacology. 1998 ; Vol. 149, No. 2. pp. 195-202.
@article{05438cd89b7f460d99edf0b70a7e248b,
title = "Cytochrome P450 2E1 in rat tracheobronchial airways: Response to ozone exposure",
abstract = "The distal trachea and centriacinus of the lung are primary sites of acute injury during short-term ozone exposure; long-term exposure yields cells in these areas that are resistant to high doses of oxidant gases. Epithelial cells located in primary sites for ozone injury are also targets for chemicals that undergo cytochrome P450 (CYP)-dependent activation. These studies were designed to compare the effects of ozone exposure on pulmonary CYP2E1 in susceptible and nonsusceptible sites within the airway tree of lung. CYP2E1 activity was measured in well-defined regions of airways using p-nitrophenol, a CYP2E1-selective substrate, with HPLC/electrochemical detection of the p-nitrocatechol. Alterations in distribution of CYP2E1 were evaluated by immunohistochemistry. CYP2E1 activities were highest in the distal bronchioles and minor daughter airways but were much lower in the lobar bronchi/major daughter airways and trachea. Immediately after short- term ozone exposures (8 h, 1 ppm), CYP2E1 activities were elevated only in the lobar bronchi/major daughter airways. These activities remained above the filtered air control at 1 day but returned to control levels by 2 days. Immunohistochemical assessment of CYP2E1 protein in ozone and filtered air- exposed animals was consistent with the activity measurements. After long- term ozone exposures (90 days, 1 ppm), CYP2E1 activities were decreased in the major and minor daughter airways. These studies indicate that CYP2E1 activities vary substantially by airway level. However, ozone exposure only results in minimal alterations in activity with varying concentration of ozone, length of exposure, and time after exposure in any of the lung subcompartments examined.",
author = "Watt, {Katherine C.} and Charles Plopper and Weir, {Alison J.} and Brian Tarkington and Buckpitt, {Alan R}",
year = "1998",
month = "4",
doi = "10.1006/taap.1998.8366",
language = "English (US)",
volume = "149",
pages = "195--202",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Cytochrome P450 2E1 in rat tracheobronchial airways

T2 - Response to ozone exposure

AU - Watt, Katherine C.

AU - Plopper, Charles

AU - Weir, Alison J.

AU - Tarkington, Brian

AU - Buckpitt, Alan R

PY - 1998/4

Y1 - 1998/4

N2 - The distal trachea and centriacinus of the lung are primary sites of acute injury during short-term ozone exposure; long-term exposure yields cells in these areas that are resistant to high doses of oxidant gases. Epithelial cells located in primary sites for ozone injury are also targets for chemicals that undergo cytochrome P450 (CYP)-dependent activation. These studies were designed to compare the effects of ozone exposure on pulmonary CYP2E1 in susceptible and nonsusceptible sites within the airway tree of lung. CYP2E1 activity was measured in well-defined regions of airways using p-nitrophenol, a CYP2E1-selective substrate, with HPLC/electrochemical detection of the p-nitrocatechol. Alterations in distribution of CYP2E1 were evaluated by immunohistochemistry. CYP2E1 activities were highest in the distal bronchioles and minor daughter airways but were much lower in the lobar bronchi/major daughter airways and trachea. Immediately after short- term ozone exposures (8 h, 1 ppm), CYP2E1 activities were elevated only in the lobar bronchi/major daughter airways. These activities remained above the filtered air control at 1 day but returned to control levels by 2 days. Immunohistochemical assessment of CYP2E1 protein in ozone and filtered air- exposed animals was consistent with the activity measurements. After long- term ozone exposures (90 days, 1 ppm), CYP2E1 activities were decreased in the major and minor daughter airways. These studies indicate that CYP2E1 activities vary substantially by airway level. However, ozone exposure only results in minimal alterations in activity with varying concentration of ozone, length of exposure, and time after exposure in any of the lung subcompartments examined.

AB - The distal trachea and centriacinus of the lung are primary sites of acute injury during short-term ozone exposure; long-term exposure yields cells in these areas that are resistant to high doses of oxidant gases. Epithelial cells located in primary sites for ozone injury are also targets for chemicals that undergo cytochrome P450 (CYP)-dependent activation. These studies were designed to compare the effects of ozone exposure on pulmonary CYP2E1 in susceptible and nonsusceptible sites within the airway tree of lung. CYP2E1 activity was measured in well-defined regions of airways using p-nitrophenol, a CYP2E1-selective substrate, with HPLC/electrochemical detection of the p-nitrocatechol. Alterations in distribution of CYP2E1 were evaluated by immunohistochemistry. CYP2E1 activities were highest in the distal bronchioles and minor daughter airways but were much lower in the lobar bronchi/major daughter airways and trachea. Immediately after short- term ozone exposures (8 h, 1 ppm), CYP2E1 activities were elevated only in the lobar bronchi/major daughter airways. These activities remained above the filtered air control at 1 day but returned to control levels by 2 days. Immunohistochemical assessment of CYP2E1 protein in ozone and filtered air- exposed animals was consistent with the activity measurements. After long- term ozone exposures (90 days, 1 ppm), CYP2E1 activities were decreased in the major and minor daughter airways. These studies indicate that CYP2E1 activities vary substantially by airway level. However, ozone exposure only results in minimal alterations in activity with varying concentration of ozone, length of exposure, and time after exposure in any of the lung subcompartments examined.

UR - http://www.scopus.com/inward/record.url?scp=0032053591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032053591&partnerID=8YFLogxK

U2 - 10.1006/taap.1998.8366

DO - 10.1006/taap.1998.8366

M3 - Article

C2 - 9571988

AN - SCOPUS:0032053591

VL - 149

SP - 195

EP - 202

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -