| First Author | Voelkl J | Year | 2016 |
| Journal | J Mol Cell Cardiol | Volume | 97 |
| Pages | 36-43 | PubMed ID | 27106803 |
| Mgi Jnum | J:250833 | Mgi Id | MGI:6102805 |
| Doi | 10.1016/j.yjmcc.2016.04.009 | Citation | Voelkl J, et al. (2016) AMP-activated protein kinase alpha1-sensitive activation of AP-1 in cardiomyocytes. J Mol Cell Cardiol 97:36-43 |
| abstractText | AMP-activated protein kinase (Ampk) regulates myocardial energy metabolism and plays a crucial role in the response to cell stress. In the failing heart, an isoform shift of the predominant Ampkalpha2 to the Ampkalpha1 was observed. The present study explored possible isoform specific effects of Ampkalpha1 in cardiomyocytes. To this end, experiments were performed in HL-1 cardiomyocytes, as well as in Ampkalpha1-deficient and corresponding wild-type mice and mice following AAV9-mediated cardiac overexpression of constitutively active Ampkalpha1. As a result, in HL-1 cardiomyocytes, overexpression of constitutively active Ampkalpha1 increased the phosphorylation of Pkczeta. Constitutively active Ampkalpha1 further increased AP-1-dependent transcriptional activity and mRNA expression of the AP-1 target genes c-Fos, Il6 and Ncx1, effects blunted by Pkczeta silencing. In HL-1 cardiomyocytes, angiotensin-II activated AP-1, an effect blunted by silencing of Ampkalpha1 and Pkczeta, but not of Ampkalpha2. In wild-type mice, angiotensin-II infusion increased cardiac Ampkalpha1 and cardiac Pkczeta protein levels, as well as c-Fos, Il6 and Ncx1 mRNA expression, effects blunted in Ampkalpha1-deficient mice. Pressure overload by transverse aortic constriction (TAC) similarly increased cardiac Ampkalpha1 and Pkczeta abundance as well as c-Fos, Il6 and Ncx1 mRNA expression, effects again blunted in Ampkalpha1-deficient mice. AAV9-mediated cardiac overexpression of constitutively active Ampkalpha1 increased Pkczeta protein abundance and the mRNA expression of c-Fos, Il6 and Ncx1 in cardiac tissue. In conclusion, Ampkalpha1 promotes myocardial AP-1 activation in a Pkczeta-dependent manner and thus contributes to cardiac stress signaling. |
