Titre :

Abnormal Mitochondrial cAMP/PKA Signaling Is Involved in Sepsis-Induced Mitochondrial and Myocardial Dysfunction.

Auteur(s) :

Nevière, Rémi [Auteur]
Faculté de Médecine Henri Warembourg - Université de Lille
Delguste, Florian [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Durand, Arthur [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Inamo, Jocelyn [Auteur]
Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique] [CHU de Martinique]
Boulanger, Eric [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Lille Inflammation Research International Center - U 995 [LIRIC]
Preau, Sebastien [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Lille Inflammation Research International Center - U 995 [LIRIC]
nevière [Auteur]

Titre de la revue :

International journal of molecular sciences

Nom court de la revue :

Int J Mol Sci

Numéro :

17

Pagination :

2075

Éditeur :

MDPI

Date de publication :

2016-12-10

ISSN :

1422-0067

Mot(s)-clé(s) :

Mesh:Mitochondrial Proteins/metabolism
Mesh:Myocardial Contraction/drug effects
Mesh:Cyclic Nucleotide Phosphodiesterases
Mesh:Type 2/metabolism
Mesh:1-Methyl-3-isobutylxanthine/pharmacology
Mesh:Animals
Mesh:Blotting
Mesh:Western
Mesh:Cell Respiration/drug effects
Mesh:Cyclic AMP/metabolism*
Mesh:Cyclic AMP-Dependent Protein Kinases/metabolism*
Mesh:Electron Transport/drug effects
Mesh:Electron Transport Complex I/metabolism
Mesh:Mice
Mesh:Mitochondria/metabolism*
Mesh:Phosphorylation/drug effects
Mesh:Triazines/pharmacology
Mesh:Phosphodiesterase Inhibitors/pharmacology
Mesh:Myocardium/pathology*
Mesh:Phosphoserine/metabolism
Mesh:Signal Transduction*/drug effects
Mesh:Sepsis/metabolism*
Mesh:Imidazoles/pharmacology
Mesh:Myocardium/metabolism*

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Adrenergic receptors couple to Gs-proteins leading to transmembrane adenylyl cyclase activation and cytosolic cyclic adenosine monophosphate (cAMP) production. Cyclic AMP is also produced in the mitochondrial matrix, where ...
Lire la suite >Adrenergic receptors couple to Gs-proteins leading to transmembrane adenylyl cyclase activation and cytosolic cyclic adenosine monophosphate (cAMP) production. Cyclic AMP is also produced in the mitochondrial matrix, where it regulates respiration through protein kinase A (PKA)-dependent phosphorylation of respiratory chain complexes. We hypothesized that a blunted mitochondrial cAMP-PKA pathway would participate in sepsis-induced heart dysfunction. Adult male mice were subjected to intra-abdominal sepsis. Mitochondrial respiration of cardiac fibers and myocardial contractile performance were evaluated in response to 8Br-cAMP, PKA inhibition (H89), soluble adenylyl cyclase inhibition (KH7), and phosphodiesterase inhibition (IBMX; BAY60-7550). Adenosine diphosphate (ADP)-stimulated respiratory rates of cardiac fibers were reduced in septic mice. Compared with controls, stimulatory effects of 8Br-cAMP on respiration rates were enhanced in septic fibers, whereas inhibitory effects of H89 were reduced. Ser-58 phosphorylation of cytochrome c oxidase subunit IV-1 was reduced in septic hearts. In vitro, incubation of septic cardiac fibers with BAY60-7550 increased respiratory control ratio and improved cardiac MVO2 efficiency in isolated septic heart. In vivo, BAY60-7550 pre-treatment of septic mice have limited impact on myocardial function. Mitochondrial cAMP-PKA signaling is impaired in the septic myocardium. PDE2 phosphodiesterase inhibition by BAY60-7550 improves mitochondrial respiration and cardiac MVO2 efficiency in septic mice.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Équipe(s) de recherche :

Glycation from inflammation to aging

Date de dépôt :

2019-03-01T14:26:04Z
2020-03-12T11:05:11Z
2022-11-16T07:26:32Z