PMID- 29436612
OWN - NLM
STAT- MEDLINE
DCOM- 20180827
LR  - 20211204
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 41
IP  - 5
DP  - 2018 May
TI  - Seawater inhalation induces acute lung injury via ROS generation and the 
      endoplasmic reticulum stress pathway.
PG  - 2505-2516
LID - 10.3892/ijmm.2018.3486 [doi]
AB  - Seawater (SW) inhalation can induce acute lung injury (ALI) and acute respiratory 
      distress syndrome (ARDS). In the present study, SW induced apoptosis of rat 
      alveolar epithelial cells and histopathological alterations to lung tissue. 
      Furthermore, SW administration increased generation of reactive oxygen 
      species (ROS), whereas pretreatment with the ROS scavenger, 
      N‑acetyl‑L‑cysteine (NAC), significantly decreased ROS generation, apoptosis and 
      histopathological alterations. In addition, SW exposure upregulated the 
      expression levels of glucose‑regulated protein 78 (GRP78) and CCAAT/enhancer 
      binding protein homologous protein (CHOP), which are critical proteins in the 
      endoplasmic reticulum (ER) stress response, thus indicating that SW may activate 
      ER stress. Conversely, blocking ER stress with 4‑phenylbutyric acid (4‑PBA) 
      significantly improved SW‑induced apoptosis and histopathological alterations, 
      whereas an ER stress inducer, thapsigargin, had the opposite effect. Furthermore, 
      blocking ROS with NAC inhibited SW‑induced ER stress, as evidenced by the 
      downregulation of GRP78, phosphorylated (p)‑protein kinase R‑like ER 
      kinase (PERK), p‑inositol‑requiring kinase 1alpha (IRE1alpha), p‑50 activating 
      transcription factor 6alpha and CHOP. In addition, blocking ER stress with 4‑PBA 
      decreased ROS generation. In conclusion, the present study indicated that ROS and 
      ER stress pathways, which are involved in alveolar epithelial cell apoptosis, are 
      important in the pathogenesis of SW‑induced ALI.
FAU - Li, Peng-Cheng
AU  - Li PC
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Wang, Bo-Rong
AU  - Wang BR
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Li, Cong-Cong
AU  - Li CC
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Lu, Xi
AU  - Lu X
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Qian, Wei-Sheng
AU  - Qian WS
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Li, Yu-Juan
AU  - Li YJ
AD  - Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, 
      Shanxi 030001, P.R. China.
FAU - Jin, Fa-Guang
AU  - Jin FG
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Mu, De-Guang
AU  - Mu DG
AD  - Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical 
      University, Xi'an, Shaanxi 710038, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180212
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - A549 Cells
MH  - Acute Lung Injury/*etiology/metabolism/*pathology
MH  - Animals
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - *Endoplasmic Reticulum Stress
MH  - Humans
MH  - Lung/metabolism/*pathology
MH  - Male
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Seawater/*adverse effects
PMC - PMC5846659
COIS- Competing interests The authors declare that they have no competing financial 
      interests.
EDAT- 2018/02/14 06:00
MHDA- 2018/08/28 06:00
PMCR- 2018/02/12
CRDT- 2018/02/14 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2018/01/12 00:00 [accepted]
PHST- 2018/02/14 06:00 [pubmed]
PHST- 2018/08/28 06:00 [medline]
PHST- 2018/02/14 06:00 [entrez]
PHST- 2018/02/12 00:00 [pmc-release]
AID - ijmm-41-05-2505 [pii]
AID - 10.3892/ijmm.2018.3486 [doi]
PST - ppublish
SO  - Int J Mol Med. 2018 May;41(5):2505-2516. doi: 10.3892/ijmm.2018.3486. Epub 2018 
      Feb 12.