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The ER stress-mediated decrease in DDAH1 expression is involved in formaldehyde-induced apoptosis in lung epithelial cells.
Food Chem Toxicol. 2013 Dec; 62:763-9.FC

Abstract

Formaldehyde (FA) is toxic to the respiratory system, and nitric oxide (NO) dysfunction stimulates the onset of respiratory diseases. The involvement of dimethylarginine dimethylaminohydrolase (DDAH), the l-arginine analogue asymmetric dimethylarginine (ADMA) degrading enzyme, in FA-induced cell death in lung epithelial cells has not been investigated. In this study, we assessed the effect of FA on DDAH expression and endoplasmic reticulum (ER) stress in A549 cells. We also investigated the preventive effect of DDAH overexpression on ER stress and apoptosis in FA-induced cell death. FA decreased viability in A549 cells and decreased DDAH1 and DDAH2 mRNA and protein expression in a time-dependent manner (>4h). This coincided with increased phosphorylation of the ER stress proteins IRE1α, PERK, and eIF-2α, as well as increased expression of pro-apoptotic proteins such as Bax, C/EPB homologous protein (CHOP), cleaved PARP, and cleaved caspase-3, but decreased expression of the anti-apoptotic protein Bcl-2. ADMA treatment mimicked the effect of FA. Overexpression of DDAH1, but not DDAH2, prevented FA-induced decreases in cell viability, phosphorylation of IRE1α, PERK, and eIF2α, and expression of CHOP. Effects of DDAH1 overexpression, but not DDAH2 overexpression, restored FA-induced increases in Bax, CHOP, cleaved PARP, cleaved caspase-3 and decreases in Bcl-2. In conclusion, FA induces apoptosis of lung epithelial cells via a decrease of DDAH1 through ER stress.

Authors+Show Affiliations

Bio-therapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24140967

Citation

Lim, Seul Ki, et al. "The ER Stress-mediated Decrease in DDAH1 Expression Is Involved in Formaldehyde-induced Apoptosis in Lung Epithelial Cells." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 62, 2013, pp. 763-9.
Lim SK, Choi H, Park MJ, et al. The ER stress-mediated decrease in DDAH1 expression is involved in formaldehyde-induced apoptosis in lung epithelial cells. Food Chem Toxicol. 2013;62:763-9.
Lim, S. K., Choi, H., Park, M. J., Kim, D. I., Kim, J. C., Kim, G. Y., Jeong, S. Y., Rodionov, R. N., Han, H. J., Yoon, K. C., & Park, S. H. (2013). The ER stress-mediated decrease in DDAH1 expression is involved in formaldehyde-induced apoptosis in lung epithelial cells. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 62, 763-9. https://doi.org/10.1016/j.fct.2013.10.014
Lim SK, et al. The ER Stress-mediated Decrease in DDAH1 Expression Is Involved in Formaldehyde-induced Apoptosis in Lung Epithelial Cells. Food Chem Toxicol. 2013;62:763-9. PubMed PMID: 24140967.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The ER stress-mediated decrease in DDAH1 expression is involved in formaldehyde-induced apoptosis in lung epithelial cells. AU - Lim,Seul Ki, AU - Choi,Hyeon, AU - Park,Min Jung, AU - Kim,Dong Il, AU - Kim,Jong Choon, AU - Kim,Gye Yeop, AU - Jeong,Soo Yeong, AU - Rodionov,Roman N, AU - Han,Ho Jae, AU - Yoon,Kyung Chul, AU - Park,Soo Hyun, Y1 - 2013/10/16/ PY - 2013/08/13/received PY - 2013/10/07/revised PY - 2013/10/09/accepted PY - 2013/10/22/entrez PY - 2013/10/22/pubmed PY - 2014/8/16/medline KW - Apoptosis KW - DDAH1 KW - DDAH2 KW - ER-stress KW - Formaldehyde KW - Lung epithelial cells SP - 763 EP - 9 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 62 N2 - Formaldehyde (FA) is toxic to the respiratory system, and nitric oxide (NO) dysfunction stimulates the onset of respiratory diseases. The involvement of dimethylarginine dimethylaminohydrolase (DDAH), the l-arginine analogue asymmetric dimethylarginine (ADMA) degrading enzyme, in FA-induced cell death in lung epithelial cells has not been investigated. In this study, we assessed the effect of FA on DDAH expression and endoplasmic reticulum (ER) stress in A549 cells. We also investigated the preventive effect of DDAH overexpression on ER stress and apoptosis in FA-induced cell death. FA decreased viability in A549 cells and decreased DDAH1 and DDAH2 mRNA and protein expression in a time-dependent manner (>4h). This coincided with increased phosphorylation of the ER stress proteins IRE1α, PERK, and eIF-2α, as well as increased expression of pro-apoptotic proteins such as Bax, C/EPB homologous protein (CHOP), cleaved PARP, and cleaved caspase-3, but decreased expression of the anti-apoptotic protein Bcl-2. ADMA treatment mimicked the effect of FA. Overexpression of DDAH1, but not DDAH2, prevented FA-induced decreases in cell viability, phosphorylation of IRE1α, PERK, and eIF2α, and expression of CHOP. Effects of DDAH1 overexpression, but not DDAH2 overexpression, restored FA-induced increases in Bax, CHOP, cleaved PARP, cleaved caspase-3 and decreases in Bcl-2. In conclusion, FA induces apoptosis of lung epithelial cells via a decrease of DDAH1 through ER stress. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/24140967/The_ER_stress_mediated_decrease_in_DDAH1_expression_is_involved_in_formaldehyde_induced_apoptosis_in_lung_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(13)00689-3 DB - PRIME DP - Unbound Medicine ER -