| First Author | Shete V | Year | 2018 |
| Journal | Int J Mol Sci | Volume | 19 |
| Issue | 12 | PubMed ID | 30469494 |
| Mgi Jnum | J:325850 | Mgi Id | MGI:6874109 |
| Doi | 10.3390/ijms19123704 | Citation | Shete V, et al. (2018) Mouse Cardiac Pde1C Is a Direct Transcriptional Target of Pparalpha. Int J Mol Sci 19(12):3704 |
| abstractText | Phosphodiesterase 1C (PDE1C) is expressed in mammalian heart and regulates cardiac functions by controlling levels of second messenger cyclic AMP and cyclic GMP (cAMP and cGMP, respectively). However, molecular mechanisms of cardiac Pde1c regulation are currently unknown. In this study, we demonstrate that treatment of wild type mice and H9c2 myoblasts with Wy-14,643, a potent ligand of nuclear receptor peroxisome-proliferator activated receptor alpha (PPARalpha), leads to elevated cardiac Pde1C mRNA and cardiac PDE1C protein, which correlate with reduced levels of cAMP. Furthermore, using mice lacking either Pparalpha or cardiomyocyte-specific Med1, the major subunit of Mediator complex, we show that Wy-14,643-mediated Pde1C induction fails to occur in the absence of Pparalpha and Med1 in the heart. Finally, using chromatin immunoprecipitation assays we demonstrate that PPARalpha binds to the upstream Pde1C promoter sequence on two sites, one of which is a palindrome sequence (agcTAGGttatcttaacctagc) that shows a robust binding. Based on these observations, we conclude that cardiac Pde1C is a direct transcriptional target of PPARalpha and that Med1 may be required for the PPARalpha mediated transcriptional activation of cardiac Pde1C. |
