TY - JOUR
T1 - Potential involvement of 4-hydroxynonenal in the response of human lung cells to ozone
AU - Hamilton, Raymond F.
AU - Li, Li
AU - Eschenbacher, William L.
AU - Szweda, Luke
AU - Holian, Andrij
PY - 1998/1
Y1 - 1998/1
N2 - Ozone is a photochemically generated pollutant that can cause acute pulmonary inflammation and induce cellular injury and may contribute to the development or exacerbation of chronic lung diseases. Despite much research, the mechanisms of ozone- and oxidant-induced cellular injury are still uncertain. Ozone and secondary free radicals have been reported to cause the formation of aldehydes in biological fluids. One of the most toxic aldehydes formed during oxidant-induced lipid peroxidation is 4-hydroxynonenal (HNE). HNE reacts primarily with Cys, Lys, and His amino acids, altering protein function and forming protein adducts. The purpose of this study was to determine whether HNE could account for the acute effects of ozone on lung cells. Human subjects were exposed to 0.4 parts/million ozone or air for 1 h with exercise (each subject served as his/her own control). Six hours after ozone exposure, cells obtained by airway lavage were examined for apoptotic cell injury, and cells from bronchoalveolar lavage were examined for apoptosis, presence of HNE adducts, and expression of stress proteins. Significant apoptosis was evident in airway lung cells after ozone exposure. Western analysis demonstrated an increase in a 32-kDa HNE protein adduct and a number of stress proteins, viz., 72-kDa heat shock protein and ferritin, in alveolar macrophages (AM) after ozone exposure. All of these effects could be replicated by in vitro exposure of AM to HNE. Consequently, the in vitro results and demonstration of HNE protein adducts after ozone exposure are consistent with a potential role for HNE in the cellular toxic effects of ozone.
AB - Ozone is a photochemically generated pollutant that can cause acute pulmonary inflammation and induce cellular injury and may contribute to the development or exacerbation of chronic lung diseases. Despite much research, the mechanisms of ozone- and oxidant-induced cellular injury are still uncertain. Ozone and secondary free radicals have been reported to cause the formation of aldehydes in biological fluids. One of the most toxic aldehydes formed during oxidant-induced lipid peroxidation is 4-hydroxynonenal (HNE). HNE reacts primarily with Cys, Lys, and His amino acids, altering protein function and forming protein adducts. The purpose of this study was to determine whether HNE could account for the acute effects of ozone on lung cells. Human subjects were exposed to 0.4 parts/million ozone or air for 1 h with exercise (each subject served as his/her own control). Six hours after ozone exposure, cells obtained by airway lavage were examined for apoptotic cell injury, and cells from bronchoalveolar lavage were examined for apoptosis, presence of HNE adducts, and expression of stress proteins. Significant apoptosis was evident in airway lung cells after ozone exposure. Western analysis demonstrated an increase in a 32-kDa HNE protein adduct and a number of stress proteins, viz., 72-kDa heat shock protein and ferritin, in alveolar macrophages (AM) after ozone exposure. All of these effects could be replicated by in vitro exposure of AM to HNE. Consequently, the in vitro results and demonstration of HNE protein adducts after ozone exposure are consistent with a potential role for HNE in the cellular toxic effects of ozone.
KW - Aldehydes
KW - Alveolar macrophages
KW - Apoptosis
KW - Protein adducts
KW - Stress proteins
UR - http://www.scopus.com/inward/record.url?scp=0031887714&partnerID=8YFLogxK
U2 - 10.1152/ajplung.1998.274.1.l8
DO - 10.1152/ajplung.1998.274.1.l8
M3 - Article
C2 - 9458795
AN - SCOPUS:0031887714
SN - 1040-0605
VL - 274
SP - L8-L16
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 1 18-1
ER -