Apoptosis induced by ozone and oxysterols in human alveolar epithelial cells.
The mechanism of ozone-induced lung cell injury is poorly understood. One hypothesis is that ozone induces lipid peroxidation and that these peroxidated lipids produce oxidative stress and DNA damage. Oxysterols are lipid peroxides formed by the direct effects of ozone on pulmonary surfactant and cell membranes. We studied the effects of ozone and the oxysterol 5beta,6beta-epoxycholesterol (beta-epoxide) and its metabolite cholestan-6-oxo-3,5-diol (6-oxo-3,5-diol) on human alveolar epithelial type I-like cells (ATI-like cells) and type II cells (ATII cells). Ozone and oxysterols induced apoptosis and cytotoxicity in ATI-like cells. They also generated reactive oxygen species and DNA damage. Ozone and beta-epoxide were strong inducers of nuclear factor erythroid 2-related factor 2, heat shock protein 70, and Fos-related antigen 1 protein expression. Furthermore, we found higher sensitivity of ATI-like cells compared to ATII cells exposed to ozone or treated with beta-epoxide or 6-oxo-3,5-diol. In general the response to the cholesterol epoxides was similar to the effect of ozone. Understanding the response of human ATI-like cells and ATII cells to oxysterols may be useful for further studies, because these compounds may represent useful biomarkers in other diseases.
Kosmider
Beata
B
Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
Loader
Joan E
JE
Murphy
Robert C
RC
Mason
Robert J
RJ
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*
C119784:5,6-epoxycholesterol; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C551154:cholestan-6-oxo-3,5-diol; D010126:Ozone; D002784:Cholesterol; D053148:Caspase 3; D053179:Caspase 7