ABSTRACT 485

Abstract

Background and aims: The production of reactive oxygen species (ROS) during hyperoxia is thought to contribute to alveolar epithelial apoptosis. Aims: To explore the molecular mechanisms of oxidative stress-induced alveolar epithelial cell apoptosis and assess the possible cytoprotective effects of N-acetylcysteine (NAC). Methods: 500 μM H2O2 treatment induced primary alveolar type II epithelial cells apoptosis, during this course a rapid increase of phosphorylation levels of JNK activated by H2O2 was found. The apoptosis of ATII cells can be prevented by SP600125, a specific inhibitor of JNK. SP600125 also attenuated Bax expression and p53 nuclear accumulation induced by H2O2. Results: Pretreatment of ATII cells with NAC (5 mM) 0.5 h before H2O2 would markedly decreased cell apoptosis and the activation of JNK. The high level of intracellular ROS induced by H2O2 was also significantly attenuated by NAC pretreatment. Conclusions: Taken together, these findings suggest JNK is the upstream of Bax and p53 in ATII cells apoptosis induced by oxidative stress, and NAC attenuated cells apoptosis through suppressing intracellular ROS generation and JNK activation.