N-acetylcysteine protects alveolar epithelial cells from hydrogen peroxide-induced apoptosis through scavenging reactive oxygen species and suppressing c-Jun N-terminal kinase.
The production of reactive oxygen species (ROS) during hyperoxia contribute to alveolar epithelial apoptosis. In the present study, the molecular mechanisms of oxidative stress-induced alveolar epithelial cell apoptosis were investigated. The cytoprotective effects of N-acetylcysteine (NAC) were evaluated. Treatments using 500 muM H(2)O(2) can induce primary alveolar type II epithelial cell apoptosis. During this procedure, c-Jun N-terminal kinase (JNK) was activated. SP600125, a specific inhibitor of JNK, can partially block H(2)O(2)-induced alveolar type II epithelial cells (ATII cells). SP600125 also attenuated Bax protein content and p53 nuclear accumulation induced by H(2)O(2). NAC (5 mM) pretreatment decreased H(2)O(2)-induced ATII cell apoptosis. The high level of intracellular reactive oxygen species (ROS) induced by H(2)O(2) was also attenuated by NAC pretreatment. Taken together, H(2)O(2) can induce primary ATII cells apoptosis and increase JNK phosphorylation. NAC, a precursor of glutathione (GSH) synthesis, can protect ATII cells from H(2)O(2)-induced apoptosis through scavenging ROS.
Fu
Yue-qiang
YQ
Department of Emergency Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.
Fang
Fang
F
Lu
Zhong-yi
ZY
Kuang
Feng-wu
FW
Xu
Feng
F
D000111:Acetylcysteine / Q000494:pharmacology*; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000873:Anthracenes; C494828:Bax protein, rat; D016166:Free Radical Scavengers; D016877:Oxidants; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione; D000111:Acetylcysteine