Premium
ERp57, an Endoplasmic Reticulum (ER) Protein, Reduces Hyperoxia‐Induced ER Stress in Lung Epithelial Cells
Author(s) -
Perez Ricardo E,
Truog William E,
Navarro Angels,
Xu Dong
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a818
Subject(s) - hyperoxia , a549 cell , endoplasmic reticulum , unfolded protein response , transfection , microbiology and biotechnology , phosphorylation , protein disulfide isomerase , chemistry , biology , cell culture , cell , biochemistry , oxygen , genetics , organic chemistry
Purpose of Study: ERp57 is an ER chaperone protein with protein disulfide isomerase activity. Our previous studies have demonstrated that hyperoxia down‐regulates ERp57 protein expression in the neonatal rat lung. In this study, we tested whether over‐expression of ERp57 in lung epithelial cells would reduce hyperoxia‐induced ER stress. Methods: Human ERp57 cDNA was subcloned into pcDNA3 plasmid and then transfected into A549 lung epithelial cells. ERp57 over‐expressing cells (ERp57‐A549) were selected by G418 and used for the experiments. Hyperoxia treatment for cultured cells was carried out in a chamber flushed with 95% O2 and 5% CO2. Results: We found that prolonged hyperoxic treatment for 24, 48 and 72 hours significantly increased phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), one of the known ER stress markers, in A549 cells. However, ERp57 over‐expression decreased hyperoxia‐induced eIF2α phosphorylation in ERp57‐A549 cells. In addition, over‐expression of human ERp57 decreased reactive oxygen species (ROS) production caused by hyperoxia, suggesting that ERp57 may be involved in regulation of cellular redox. Conclusions: Our results reveal that hyperoxia induces eIF2α phosphorylation and ER stress. Over‐expression of ERp57 in human lung epithelial cells reduces ROS generation and ER stress under hyperoxic condition.