Impaired SIRT3 activity mediates cardiac dysfunction in endotoxemia by calpain-dependent disruption of ATP synthesis.
Adenosine Triphosphate
/ biosynthesis
Animals
Calpain
/ antagonists & inhibitors
Cytokines
Disease Models, Animal
Endotoxemia
/ complications
Enzyme Activation
Heart Diseases
/ etiology
Humans
Male
Mice
Mice, Knockout
Mitochondria, Heart
/ metabolism
Myocytes, Cardiac
/ metabolism
Oxidative Stress
Sepsis
/ complications
Signal Transduction
Sirtuin 3
/ genetics
Cardiomyopathy
Metabolism
Pathophysiology
Journal
Journal of molecular and cellular cardiology
ISSN: 1095-8584
Titre abrégé: J Mol Cell Cardiol
Pays: England
ID NLM: 0262322
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
14
12
2018
revised:
07
02
2019
accepted:
12
06
2019
pubmed:
16
6
2019
medline:
26
6
2020
entrez:
16
6
2019
Statut:
ppublish
Résumé
Sepsis-induced cardiomyopathy contributes to the high mortality of septic shock in critically ill patients. Since the underlying mechanisms are incompletely understood, we hypothesized that sepsis-induced impairment of sirtuin 3 (SIRT3) activity contributes to the development of septic cardiomyopathy. Treatment of mice with lipopolysaccharide (LPS) for 6 h resulted in myocardial NAD Impaired SIRT3 activity may mediate cardiac dysfunction in endotoxemia by facilitating calpain-mediated disruption of ATP synthesis, suggesting SIRT3 activation as a potential therapeutic strategy to treat septic cardiomyopathy.
Sections du résumé
BACKGROUND
Sepsis-induced cardiomyopathy contributes to the high mortality of septic shock in critically ill patients. Since the underlying mechanisms are incompletely understood, we hypothesized that sepsis-induced impairment of sirtuin 3 (SIRT3) activity contributes to the development of septic cardiomyopathy.
METHODS AND RESULTS
Treatment of mice with lipopolysaccharide (LPS) for 6 h resulted in myocardial NAD
CONCLUSIONS
Impaired SIRT3 activity may mediate cardiac dysfunction in endotoxemia by facilitating calpain-mediated disruption of ATP synthesis, suggesting SIRT3 activation as a potential therapeutic strategy to treat septic cardiomyopathy.
Identifiants
pubmed: 31201798
pii: S0022-2828(18)31292-6
doi: 10.1016/j.yjmcc.2019.06.008
pii:
doi:
Substances chimiques
Cytokines
0
Adenosine Triphosphate
8L70Q75FXE
Calpain
EC 3.4.22.-
Sirtuin 3
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-147Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.