Augmented Parkin-dependent mitophagy underlies the hepatoprotective effect of remote ischemic conditioning used prior to hemorrhagic shock.
Hemorrhagic shock-resuscitation
Ischemia–reperfusion injury
Mitochondria
Mitochondrial quality control
Parkin-dependent mitophagy
Journal
Mitochondrion
ISSN: 1872-8278
Titre abrégé: Mitochondrion
Pays: Netherlands
ID NLM: 100968751
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
23
10
2022
revised:
04
02
2023
accepted:
05
03
2023
medline:
22
5
2023
pubmed:
12
3
2023
entrez:
11
3
2023
Statut:
ppublish
Résumé
Hemorrhagic shock-resuscitation (HSR) following trauma contributes to organ dysfunction by causing ischemia-reperfusion injury (IRI). We previously showed that 'remote ischemic preconditioning' (RIPC) exerted multi-organ protection from IRI. Maintenance of mitochondrial quality by clearance of dysfunctional mitochondria via mitophagy is vital in restoring organ integrity. We hypothesized that parkin-dependent mitophagy played a role in RIPC-induced hepatoprotection following HSR. The hepatoprotective effect of RIPC in a murine model of HSR-IRI was investigated in wild type and parkin-/- animals. Mice were subjected to HSR ± RIPC and blood and organs were collected, followed by cytokine ELISAs, histology, qPCR, Western blots, and transmission electron microscopy. HSR increased hepatocellular injury, as measured by plasma ALT and liver necrosis, while antecedent RIPC prevented this injury; in parkin RIPC was hepatoprotective in WT mice following HSR but not in parkin
Sections du résumé
BACKGROUND AND AIMS
Hemorrhagic shock-resuscitation (HSR) following trauma contributes to organ dysfunction by causing ischemia-reperfusion injury (IRI). We previously showed that 'remote ischemic preconditioning' (RIPC) exerted multi-organ protection from IRI. Maintenance of mitochondrial quality by clearance of dysfunctional mitochondria via mitophagy is vital in restoring organ integrity. We hypothesized that parkin-dependent mitophagy played a role in RIPC-induced hepatoprotection following HSR.
METHODS
The hepatoprotective effect of RIPC in a murine model of HSR-IRI was investigated in wild type and parkin-/- animals. Mice were subjected to HSR ± RIPC and blood and organs were collected, followed by cytokine ELISAs, histology, qPCR, Western blots, and transmission electron microscopy.
RESULTS
HSR increased hepatocellular injury, as measured by plasma ALT and liver necrosis, while antecedent RIPC prevented this injury; in parkin
CONCLUSIONS
RIPC was hepatoprotective in WT mice following HSR but not in parkin
Identifiants
pubmed: 36906251
pii: S1567-7249(23)00028-4
doi: 10.1016/j.mito.2023.03.002
pii:
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20-30Subventions
Organisme : CIHR
ID : 23766
Pays : Canada
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.