Cadmium-induced apoptosis of primary epithelial lung cells: involvement of Bax and p53, but not of oxidative stress.
The lung is a target organ for cadmium (Cd) toxicity. Apoptosis induced by cadmium acetate (CdAc) was studied in alveolar type 2 cells and Clara cells isolated from rat lung. Relatively low concentrations of CdAc (1-10 micromol/L) induced apoptosis after exposure for 20 h. Type 2 cells were more sensitive than Clara cells to Cd-induced apoptosis and loss of cell viability. On exposure to 10 micromol/L CdAc, the levels of the apoptosis-modulating proteins p53 and Bax were increased at 2 h and 5-12 h, respectively. The expression of p53 preceded the expression of Bax and the apoptotic process. The exposure to 10 micromol/L CdAc did not significantly increase the formation of cellular reactive oxygen species (ROS). However, after exposure to a high concentration of CdAc (100 micromol/L), a 30% increase of the ROS level was observed. No significant nitric oxide production was measured following CdAc exposure. Catalase, superoxide dismutase, dimethyl sulfoxide, or tetramethylthiourea did not protect against Cd-induced apoptosis. In conclusion, the results show that Clara cells and type 2 cells are sensitive to Cd-induced apoptosis. Increased levels of p53 and Bax are suggested to be involved in the apoptosis. The apoptosis did not appear to be mediated by oxidative pathways.
Lag
M
M
Department of Environmental Medicine, National Institute of Public Health, Nydalen, Oslo, Norway. marit.lag@folkehelsa.no
Westly
S
S
Lerstad
T
T
Bjørnsrud
C
C
Refsnes
M
M
Schwarze
P E
PE
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein
D000085:Acetates; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002104:Cadmium; D009569:Nitric Oxide; C028031:cadmium acetate