Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion.
acute kidney failure
ischemia-reperfusion injury
mitochondrial dysfunction
pyruvate dehydrogenase kinase 4
reactive oxygen species
succinate accumulation
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
07
08
2022
revised:
26
05
2023
accepted:
02
06
2023
medline:
25
9
2023
pubmed:
4
7
2023
entrez:
3
7
2023
Statut:
ppublish
Résumé
Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by its oxidation during reperfusion leads to excessive reactive oxygen species (ROS) and severe kidney damage. Consequently, the targeting of succinate accumulation may represent a rational approach to the prevention of IR-induced kidney injury. Since ROS are generated primarily in mitochondria, which are abundant in the proximal tubule of the kidney, we explored the role of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme, in IR-induced kidney injury using proximal tubule cell-specific Pdk4 knockout (Pdk4
Identifiants
pubmed: 37399974
pii: S0085-2538(23)00477-5
doi: 10.1016/j.kint.2023.06.022
pii:
doi:
Substances chimiques
Succinic Acid
AB6MNQ6J6L
pyruvate dehydrogenase kinase 4
EC 2.7.1.-
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
724-739Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.