ER stress preconditioning ameliorates liver damage after hemorrhagic shock and reperfusion.
binding immunoglobulin protein
hemorrhage
ischemia-reperfusion injury
tunicamycin
unfolded protein response
Journal
Experimental and therapeutic medicine
ISSN: 1792-0981
Titre abrégé: Exp Ther Med
Pays: Greece
ID NLM: 101531947
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
02
07
2020
accepted:
28
10
2020
entrez:
19
2
2021
pubmed:
20
2
2021
medline:
20
2
2021
Statut:
ppublish
Résumé
The mismatch of oxygen supply and demand during hemorrhagic shock disturbs endoplasmic reticulum (ER) homeostasis. The resulting accumulation of unfolded proteins in the ER lumen, which is a condition that is defined as ER stress, triggers the unfolded protein response (UPR). Since the UPR influences the extent of organ damage following hemorrhagic shock/reperfusion (HS/R) and mediates the protective effects of stress preconditioning before ischemia-reperfusion injury, the current study investigated the mechanisms of ER stress preconditioning and its impact on post-hemorrhagic liver damage. Male C56BL/6-mice were injected intraperitoneally with the ER stress inductor tunicamycin (TM) or its drug vehicle 48 h prior to being subjected to a 90 min pressure-controlled hemorrhagic shock (30±5 mmHg). A period of 14 h after hemorrhagic shock induction, mice were sacrificed. Hepatocellular damage was quantified by analyzing hepatic transaminases and hematoxylin-eosin stained liver tissue sections. Additionally, the topographic expression patterns of the ER stress marker binding immunoglobulin protein (BiP), UPR signaling pathways, and the autophagy marker Beclin1 were evaluated. TM injection significantly increased BiP expression and modified the topographic expression patterns of the UPR signaling proteins. In addition, immunohistochemical analysis of Beclin1 revealed an increased pericentral staining intensity following TM pretreatment. The histologic analysis of hepatocellular damage demonstrated a significant reduction in cell death areas in HS/R+TM (P=0.024). ER stress preconditioning influences the UPR and alleviates post-hemorrhagic liver damage. The beneficial effects were, at least partially, mediated by the upregulation of BiP and autophagy induction. These results underscore the importance of the UPR in the context of HS/R and may help identify novel therapeutic targets.
Identifiants
pubmed: 33603856
doi: 10.3892/etm.2021.9679
pii: ETM-0-0-09679
pmc: PMC7851603
doi:
Types de publication
Journal Article
Langues
eng
Pagination
248Informations de copyright
Copyright: © Obert et al.
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