Overexpression of ankyrin repeat domain 1 enhances cardiomyocyte apoptosis by promoting p53 activation and mitochondrial dysfunctionin in rodents

The gene ankyrin repeat domain 1 (Ankrd1) is known to upregulate in heart failure and acts as a co-activator of p53 and modulates its transcriptional activity, but it remains inconclusive whether this gene promotes or inhibits cell apoptosis. Here we attempted to investigate the role of Ankrd1 on angiotensin II- or pressure overload-induced cardiomyocyte apoptosis. In the failing hearts of mice with pressure overload or myocardial infarction, the protein expression of Ankrd1 termed cardiac ankyrin repeat protein (CARP) was significantly increased. In neonatal rat cardiomyocytes (NRCs), angiotensin II (Ang II) increased the expression of Ankrd1 and CARP. In the presence of Ang-II in NRCs, infection with a recombinant adenovirus containing rat Ankrd1 cDNA (Ad-Ankrd1) enhanced the mitochondrial translocation of Bax, upregulation of phosphorylated p53 in mitochondria and nuclei, increased mitochondrial permeability and cardiomyocyte apoptosis, and reducing cell viability, while these effects were antagonized by silencing of Ankrd1. Intra-myocardial injection of Ad-Ankrd1 in mice with transverse aortic constriction (TAC) markedly exacerbated cardiac dysfunction with an increase of the lung weight/body weight ratio and a decrease of left ventricular fractional shortening. Cardiomyocyte apoptosis and the expression of phosphorylated p53 were also significantly increased in Ad-Ankrd1-infected TAC mice, whereas knockdown of Ankrd1 significantly inhibited apoptotic signal pathway as we...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research