Heme Oxygenase-1 Reduces Sepsis-Induced Endoplasmic Reticulum Stress and Acute Lung Injury.
Mediators Inflamm
; 2018: 9413876, 2018.
Article
em En
| MEDLINE
| ID: mdl-30013453
ABSTRACT
BACKGROUND:
Sepsis leads to severe acute lung injury/acute respiratory distress syndrome (ALI/ARDS) that is associated with enhanced endoplasmic reticulum (ER) stress. Heme oxygenase-1 (HO-1), an ER-anchored protein, exerts antioxidant and protective functions under ALI. However, the role of HO-1 activation in the development of endoplasmic reticulum (ER) stress during sepsis remains unknown.METHODS:
Cecal ligation and puncture (CLP) model was created to induce septic ALI. Lung tissue ER stress was measured 18 hours after CLP. The effects of HO-1 on ER stress during septic ALI were investigated in vivo using HO-1 agonist hemin and antagonist ZnPP.RESULTS:
Compared with the sham group, ER stress in septic lung increased significantly 18 hours after CLP, which was significantly reduced by pretreatment with the ER inhibitor 4-phenylbutyrate (4-PBA). The lung injury score and the lung wet to dry (W/D) ratio in lungs were significantly reduced in septic rats after ER stress inhibition. Similarly, lung ER stress-related genes' (PERK, eIF2-α, ATF4, and CHOP) levels were attenuated after ER stress inhibition. Furthermore, HO-1 activation by hemin reduced p-PERK, p-eIF2-α, ATF4, and CHOP protein expression and oxidative stress and lung cell apoptosis. Additionally, HO-1 antagonist could aggregate the ER stress-related ALI.CONCLUSIONS:
ER stress was activated during CLP-induced ALI, which may represent a mechanism by which CLP induces ALI. HO-1 activation could inhibit CLP-induced lung ER stress and attenuate CLP-induced ALI.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sepse
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Retículo Endoplasmático
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Lesão Pulmonar Aguda
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Estresse do Retículo Endoplasmático
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Heme Oxigenase (Desciclizante)
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China