Mice deficient in pyruvate dehydrogenase kinase 4 are protected against acetaminophen-induced hepatotoxicity.
Acetaminophen
/ poisoning
Animals
Chemical and Drug Induced Liver Injury
/ etiology
Disease Models, Animal
Drug Overdose
/ complications
Energy Metabolism
/ drug effects
Female
Humans
Liver
/ cytology
Male
Mice
Mice, Knockout
Mitochondria
/ drug effects
Oxidative Stress
/ drug effects
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
/ genetics
Uncoupling Protein 2
/ metabolism
Acetaminophen, drug-induced liver injury
Bioenergetics
Mitochondria
Oxidant stress
UCP2
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
23
08
2019
revised:
22
11
2019
accepted:
02
12
2019
pubmed:
7
12
2019
medline:
22
8
2020
entrez:
7
12
2019
Statut:
ppublish
Résumé
Though mitochondrial oxidant stress plays a critical role in the progression of acetaminophen (APAP) overdose-induced liver damage, the influence of mitochondrial bioenergetics on this is not well characterized. This is important, since lifestyle and diet alter hepatic mitochondrial bioenergetics and an understanding of its effects on APAP-induced liver injury is clinically relevant. Pyruvate dehydrogenase (PDH) is critical to mitochondrial bioenergetics, since it controls the rate of generation of reducing equivalents driving respiration, and pyruvate dehydrogenase kinase 4 (PDK4) regulates (inhibits) PDH by phosphorylation. We examined APAP-induced liver injury in PDK4-deficient (PDK4
Identifiants
pubmed: 31809757
pii: S0041-008X(19)30457-0
doi: 10.1016/j.taap.2019.114849
pmc: PMC6995777
mid: NIHMS1546522
pii:
doi:
Substances chimiques
Pdk4 protein, mouse
0
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
0
Ucp2 protein, mouse
0
Uncoupling Protein 2
0
Acetaminophen
362O9ITL9D
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114849Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM118247
Pays : United States
Organisme : NIDDK NIH HHS
ID : F31 DK120194
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103549
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102142
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119131
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. 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.
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