| First Author | Mahmoodzadeh S | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 96 |
| Issue | 3 | Pages | 411-21 |
| PubMed ID | 22962310 | Mgi Jnum | J:325790 |
| Mgi Id | MGI:6872511 | Doi | 10.1093/cvr/cvs281 |
| Citation | Mahmoodzadeh S, et al. (2012) 17beta-Estradiol-induced interaction of ERalpha with NPPA regulates gene expression in cardiomyocytes. Cardiovasc Res 96(3):411-21 |
| abstractText | AIMS: 17beta-Oestradiol (E2) and its receptors (ERalpha and ERbeta) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not fully elucidated. To gain better understanding of E2-induced ERalpha action in the human heart, we aimed to identify and functionally analyse interaction partners of ERalpha. METHODS AND RESULTS: Using yeast two-hybrid assays with a human heart cDNA library, we identified atrial natriuretic peptide precursor A (NPPA), a well-known cardiac hypertrophy marker, as a novel ERalpha interaction partner interacting in an E2-dependent manner. Mutation analyses and immunofluorescence data indicated that the LXXLL motif within NPPA is necessary for its E2-induced interaction with ERalpha, its action as a co-repressor of ERalpha, and its translocation into the nucleus of human and rat cardiomyocytes. Expression analysis and chromatin immunoprecipitation assays in a human left ventricular cardiomyocyte cell line, AC16, showed that NPPA interacts with E2/ERalpha, suppressing the transcriptional activity of ERalpha on E2-target genes, such as NPPA, connexin43, alphaactinin-2, nuclear factor of activated T-cells, and collagens I and III. CONCLUSION: We characterize for the first time an E2-regulated interaction of NPPA with ERalpha in cardiomyocytes, that may be crucial in physiological and/or pathological cardiac processes, thereby representing a potential therapeutic target. |
