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Song, Yang, Jeong, Park, Jee, Kim, and Lee: Paraquat-Induced Apoptotic Cell Death in Lung Epithelial Cells
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2006; 61(4): 366-373.

Published online: 31 October 2006

DOI: https://doi.org/10.4046/trd.2006.61.4.366

Paraquat-Induced Apoptotic Cell Death in Lung Epithelial Cells

Tak Ho Song, M.D., Joo Yeon Yang, M.D., In Kook Jeong, M.D., Jae Seok Park, M.D., Young Koo Jee, M.D., Youn Seup Kim, M.D., Kye Young Lee, M.D.1

Department of Internal Medicine, College of Medicine, Dankook University, Cheonan, Korea.

1Department of Internal Medicine, Konkuk University Hospital School of Medicine, Konkuk University, Seoul, Korea.

Address for correspondence: Kye Young Lee, M.D. Department of Internal medicine, Konkuk University Hospital School of Medicine, Konkuk University 4-12, Hwayang-Dong, Gwangjin-Gu, Seoul, 143-914, Korea. Phone: 82-2-2030-7521, Fax: +82-2-2030-7748, kyleemd@kuh.ac.kr

Received 7 August 2006       Accepted 21 September 2006

Copyright © 2006 The Korean Academy of Tuberculosis and Respiratory Diseases

Abstract

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.

Keywords: Paraquat, Apoptosis, Bcl-2, N-acetylcysteine, Dexamethasone

Figures and Tables

Figure 1-A
MTT assay for paraquat-induced cell deaths in A549 cells
trd-61-366-g001
Figure 1-B
MTT assay for paraquat-induced cell deaths in BEAS-2B cells
trd-61-366-g002
Figure 3
Inhibition of paraquat-induced cell deaths by NAC (NAC : N-acetylcysteine)
trd-61-366-g003
Figure 4
Inhibition of paraquat-induced cell deaths by dexamethasone
trd-61-366-g004
Figure 5
The role of bcl-2 in paraquat-induced cell deaths (Inhibition of paraquat-induced cell deaths by bcl-2 overexpression)
trd-61-366-g005
Table 1-A
MTT assay for paraquat-induced cell deaths in A549 cells
trd-61-366-i001

PQ : paraquat

Data are the means ± SD.uat

Table 1-B
MTT assay for paraquat-induced cell deaths in BEAS-2B cells
trd-61-366-i002

PQ : paraquat

Data are the means ± SD.

Table 2
The paraquat-induced between apoptotic cells death and necrotic cells death in A549 cells by Annexin-V assay.
trd-61-366-i003

PQ : paraquat

Data are the means ± SD.

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