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mTOR inactivation in myocardium from infant mice rapidly leads to dilated cardiomyopathy due to translation defects and p53/JNK-mediated apoptosis by Laetitia Mazelin; Baptiste Panthu; Anne-Sophie Nicot; Edwige Belotti; Lionel Tintignac; Geoffrey Teixeira; Qing Zhang; Valérie Risson; Dominique Baas; Emilie Delaune; Geneviève Derumeaux; Daniel Taillandier; Théophile Ohlmann; Michel Ovize; Yann-Gaël Gangloff; Laurent Schaeffer is a Medicine article available to read on EtoBox.

What is mTOR inactivation in myocardium from infant mice rapidly leads to dilated cardiomyopathy due to translation defects and p53/JNK-mediated apoptosis about?

Mechanistic target of rapamycin (mTOR) is a central regulator of cell growth, proliferation, survival and metabolism, as part of mTOR complex 1 (mTORC1) and mTORC2. While partial inhibition of mTORC1 using rapamycin was shown to be cardioprotective, genetic studies in mouse models revealed that mTOR is essential for embryonic heart development and cardiac function in adults. However, the physiological role of mTOR during postnatal cardiac maturation is not fully elucidated. We have therefore generated a mouse model in which cardiac mTOR was inactivated at an early postnatal stage. Mutant mTORcmKO mice rapidly developed a dilated cardiomyopathy associated with cardiomyocyte growth defects, apoptosis and fibrosis, and died during their third week. Here, we show that reduced cardiomyocyte growth results from impaired protein translation efficiency through both 4E-BP1-dependent and -independent mechanisms. In addition, infant mTORcmKO hearts displayed markedly increased apoptosis linked to stretch-induced ANKRD1 (Ankyrin repeat-domain containing protein 1) up-regulation, JNK kinase activation and p53 accumulation. Pharmacological inhibition of p53 with pifithrin-α attenuated caspase-3

Who reads mTOR inactivation in myocardium from infant mice rapidly leads to dilated cardiomyopathy due to translation defects and p53/JNK-mediated apoptosis?

Author

Laetitia Mazelin; Baptiste Panthu; Anne-Sophie Nicot; Edwige Belotti; Lionel Tintignac; Geoffrey Teixeira; Qing Zhang; Valérie Risson; Dominique Baas; Emilie Delaune; Geneviève Derumeaux; Daniel Taillandier; Théophile Ohlmann; Michel Ovize; Yann-Gaël Gangloff; Laurent Schaeffer

Publisher

Elsevier BV

Published

2016

Language

EN

Field

Medicine (Health Sciences)