Seawater inhalation induces acute lung injury via ROS generation and the endoplasmic reticulum stress pathway.
Int J Mol Med
; 41(5): 2505-2516, 2018 May.
Article
em En
| MEDLINE
| ID: mdl-29436612
ABSTRACT
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, NacetylLcysteine (NAC), significantly decreased ROS generation, apoptosis and histopathological alterations. In addition, SW exposure upregulated the expression levels of glucoseregulated 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 4phenylbutyric acid (4PBA) significantly improved SWinduced apoptosis and histopathological alterations, whereas an ER stress inducer, thapsigargin, had the opposite effect. Furthermore, blocking ROS with NAC inhibited SWinduced ER stress, as evidenced by the downregulation of GRP78, phosphorylated (p)protein kinase Rlike ER kinase (PERK), pinositolrequiring kinase 1α (IRE1α), p50 activating transcription factor 6α and CHOP. In addition, blocking ER stress with 4PBA 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 SWinduced ALI.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Água do Mar
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Espécies Reativas de Oxigênio
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Lesão Pulmonar Aguda
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Estresse do Retículo Endoplasmático
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Pulmão
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article