Paraquat-Induced Apoptotic Cell Death in Lung Epithelial Cells

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type Ⅱ pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; ⅰ) whether or not paraquat induces cell death in lung epithelial cells; ⅱ) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and ⅲ) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin Ⅴ staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin Ⅴ assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway. (Tuberc Respir Dis 2006; 61: 366-373)

keywords: Paraquat, Apoptosis, Bcl-2, N-acetylcysteine, Dexamethasone., Paraquat, Apoptosis, Bcl-2, N-acetylcysteine, Dexamethasone.

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Article Contents

Vol.61 No.4

Paraquat-Induced Apoptotic Cell Death in Lung Epithelial Cells

Abstract

Reference

Tuberculosis & Respiratory Diseases