Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_05FAE4F5D489
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.
Périodique
PLoS One
Auteur(s)
Nagata T., Yasukawa H., Kyogoku S., Oba T., Takahashi J., Nohara S., Minami T., Mawatari K., Sugi Y., Shimozono K., Pradervand S., Hoshijima M., Aoki H., Fukumoto Y., Imaizumi T.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2015
Volume
10
Numéro
5
Pages
e0127942
Langue
anglais
Résumé
Myocardial ischemia reperfusion injury (IRI) adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT) 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS)-3, an intrinsic negative feedback regulator of the Janus kinase (JAK)-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO). The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.
Mots-clé
Animals, Gene Deletion, MAP Kinase Signaling System, Mice, Mice, Knockout, Mitogen-Activated Protein Kinase 3/genetics, Mitogen-Activated Protein Kinase 3/metabolism, Muscle Proteins/genetics, Muscle Proteins/metabolism, Myeloid Cell Leukemia Sequence 1 Protein/genetics, Myeloid Cell Leukemia Sequence 1 Protein/metabolism, Myocardial Reperfusion Injury/genetics, Myocardial Reperfusion Injury/metabolism, Myocardium/metabolism, Myocardium/pathology, Phosphorylation/genetics, Proto-Oncogene Proteins c-akt/genetics, Proto-Oncogene Proteins c-akt/metabolism, Suppressor of Cytokine Signaling Proteins/genetics, Suppressor of Cytokine Signaling Proteins/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/07/2016 9:19
Dernière modification de la notice
20/08/2019 12:28
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