Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

ABSTRACT:

Background

The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure.

Methods and results

Consistent with its ability to inhibit prolyl-tRNA synthetase, halofuginone elicited a general control nonderepressible 2-depe

SUBMITTER: Qin P 

PROVIDER: S-EPMC5524058 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature