N-acetylcysteine protects alveolar epithelial cells from hydrogen peroxide–induced apoptosis through scavenging reactive oxygen species and suppressing c-Jun N-terminal kinase

ABSTRACT

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 μM H₂O₂ 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 H₂O₂-induced alveolar type II epithelial cells (ATII cells). SP600125 also attenuated Bax protein content and p53 nuclear accumulation induced by H₂O₂. NAC (5 mM) pretreatment decreased H₂O₂-induced ATII cell apoptosis. The high level of intracellular reactive oxygen species (ROS) induced by H₂O₂ was also attenuated by NAC pretreatment. Taken together, H₂O₂ can induce primary ATII cells apoptosis and increase JNK phosphorylation. NAC, a precursor of glutathione (GSH) synthesis, can protect ATII cells from H₂O₂-induced apoptosis through scavenging ROS.

KEYWORDS :

• alveolar type II epithelial cells
• apoptosis
• cytoprotective properties
• JNK
• NAC
• reactive oxygen species