[Apoptosis of alveolar type II epithelial cells regulated by extracellular signal-regulated kinase under oxidative stress].
OBJECTIVE
To investigate survival and apoptotic responses of alveolar type II epithelial cells (AT II cells) under oxidative stress and the regulation mechanism mediated by extracellular signal-regulated kinase (ERK).


METHODS
Primary passage of cultured rat AT II cells were challenged with hydrogen peroxide (H(2)O(2)), and the cells were pretreated with specific inhibitor of ERK (PD 98059) in another group. Cell viability, apoptotic rate and the expression of phosphorylated ERK1/2 (p-ERK1/2)were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and Western blotting analysis, respectively.


RESULTS
Compared with control group, decreased cell viability and increased apoptotic rate in AT II cells occurred in dose-dependent manner when treated with H(2)O(2) 500 and 1,000 micromol/L (all P<0.05), but no differences were found when H(2)O(2) were 10 and 100 micromol/L in concentrations. When the cells were treated with 500 micromol/L H(2)O(2) for 30 minutes, no differences in cell viability and apoptotic rate were found compared with control group,but reduced cell viability and increased apoptotic rate were found when the duration was 180 minutes, and it was in time-dependent manner (both P<0.05). The expression of p-ERK peaked at 30 minutes after stimulation by 500 micromol/L H(2)O(2). When PD 98059 was added, it enhanced apoptotic rate after H(2)O(2)-exposure.


CONCLUSIONS
Apoptosis can be induced by H(2)O(2) in AT II cells in dose-and time-dependent manners. ERK signaling pathway plays a role in the regulation of apoptosis and may be protective for AT II cells under oxidative stress.
Chen
Juan
J
Intensive Care Unit, Children's Hospital, Chongqing University of Medical Sciences, Chongqing, China.
Xu
Feng
F
Jiang
Jing
J
Fang
Fang
F
Kuang
Feng-Wu
FW
Lu
Zhong-Yi
ZY
Wang
Xing-Yong
XY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005419:Flavonoids; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one