Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy.

Détails

ID Serval
serval:BIB_92D0FC76BDAE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy.
Périodique
Cardiovascular Research
Auteur(s)
Shende P., Xu L., Morandi C., Pentassuglia L., Heim P., Lebboukh S., Berthonneche C., Pedrazzini T., Kaufmann B.A., Hall M.N., Rüegg M.A., Brink M.
ISSN
1755-3245 (Electronic)
ISSN-L
0008-6363
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
109
Numéro
1
Pages
103-114
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
AIMS: Mammalian target of rapamycin (mTOR), a central regulator of growth and metabolism, has tissue-specific functions depending on whether it is part of mTOR complex 1 (mTORC1) or mTORC2. We have previously shown that mTORC1 is required for adaptive cardiac hypertrophy and maintenance of function under basal and pressure-overload conditions. In the present study, we aimed to identify functions of mTORC2 in the heart.
METHODS AND RESULTS: Using tamoxifen-inducible cardiomyocyte-specific gene deletion, we generated mice deficient for cardiac rapamycin-insensitive companion of mTOR (rictor), an essential and specific component of mTORC2. Under basal conditions, rictor deficiency did not affect cardiac growth and function in young mice and also had no effects in adult mice. However, transverse aortic constriction caused dysfunction in the rictor-deficient hearts, whereas function was maintained in controls after 1 week of pressure overload. Adaptive increases in cardiac weight and cardiomyocyte cross-sectional area, fibrosis, and hypertrophic and metabolic gene expression were not different between the rictor-deficient and control mice. In control mice, maintained function was associated with increased protein levels of rictor, protein kinase C (PKC)βII, and PKCδ, whereas rictor ablation abolished these increases. Rictor deletion also significantly decreased PKCε at baseline and after pressure overload. Our data suggest that reduced PKCε and the inability to increase PKCβII and PKCδ abundance are, in accordance with their known function, responsible for decreased contractile performance of the rictor-deficient hearts.
CONCLUSION: Our study demonstrates that mTORC2 is implicated in maintaining contractile function of the pressure-overloaded male mouse heart.
Mots-clé
Animals, Apoptosis, Cardiomegaly/physiopathology, Carrier Proteins/physiology, Fibrosis, Male, Mice, Mice, Inbred C57BL, Multiprotein Complexes/physiology, Myocardium/pathology, Phosphoproteins/physiology, Phosphorylation, Protein Kinase C/analysis, Proto-Oncogene Proteins c-akt/metabolism, Signal Transduction, TOR Serine-Threonine Kinases/physiology, Ventricular Function/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/10/2016 16:29
Dernière modification de la notice
08/05/2019 22:07
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