ER stress is activated by SW. Time-dependent effects of SW on the ER stress-associated proteins GRP78 and CHOP in (A) rat lungs and (B) A549 cells. A549 cells or rats were treated with SW for the indicated ti mes, and the expression levels of GRP78 and CHOP were assessed by western blot analysis. (C) Effects of ER stress inhibitors or activators on SW-induced ER stress in A549 cells. Following pretreatment with 2 mM 4-PBA or 150 nM Thap alone as the positive control of SW for 2 h, A549 cells were treated with 25% SW for 4 h, and the expression of ER stress-associated proteins was assessed. (D) Effects of ER stress inhibitors on SW-induced ER stress in rat lungs. Following pretreatment with 4-PBA (30 mg/kg), the rats were treated with SW for 4 h, and immunohistochemistry was used to detect GRP78 expression in rat lungs. (a) Control, (b) SW, (c) 4-PBA and (d) 4-PBA + SW groups (magnification, ×10). Data are presented as the means ± standard error of the mean, n=5. **P<0.01 and ***P<0.001 vs. the control group; #P<0.05 and ##P<0.01 vs. the SW group; ^^^P<0.001 vs. 4-PBA group. 4-PBA, 4-phenylbutyric acid; CHOP, CCAAT/enhancer binding protein homologous protein; ER, endoplasmic reticulum; SW, seawater; Thap, thapsigargin.