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cAMP-Dependent Protein Kinase A-Stimulated Sarcoplasmic Reticulum Function in Heart Failurea
| Content Provider | Scilit |
|---|---|
| Author | Schwinger, Robert H. G. Bolck, Birgit Munch, Gotz Brixius, Klara Muller-Ehmsen, Jochen Erdmann, Erland |
| Copyright Year | 1998 |
| Description | Journal: Annals of the New York Academy of Sciences It is unclear whether decreased protein expression of SERCA2 $(sr‐Ca^{2+}$‐ATPase) and phospholamban (PLB), or alterations in the phosphorylation state of PLB leading to increased inhibition of SERCA2 are responsible for the reduced SERCA2 function in failing human myocardium. In crude membrane preparations from patients with terminal heart failure due to idiopathic dilated cardiomyopathy (DCM) and control hearts (NF), SERCA2 activity was measured with a NADH coupled assay. Protein expression of SERCA2 and PLB and the phosphorylation state at the two phosphorylation sites, serine‐16‐PLB and threonine‐17‐PLB, were investigated with specific (phosphorylation) antibodies and Western blot technique. In NF, the $V_{max}$ and the $Ca^{2+}$ sensitivity of SERCA2 activity were significantly higher compared to DCM. Protein expression of SERCA2 and PLB were unchanged, whereas the phosphorylation status at both serine‐16‐PLB and threonine‐17‐PLB were significantly reduced in DCM. The native phosphorylation status of PLB measured by the back‐phosphorylation technique was reduced in DCM as well. After stimulation with protein kinase A only the $Ca^{2+}$ sensitivity, but not $V_{max}$, increased. The reduced phosphorylation state of PLB may lead to decreased $Ca^{2+}$ sensitivity of SERCA2 in failing human myocardium. The altered regulation of the $SR‐Ca^{2+}$‐ATPase in human heart failure may offer an opportunity for an improvement in the therapy of heart failure. |
| Related Links | https://nyaspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1749-6632.1998.tb08272.x |
| Ending Page | 250 |
| Page Count | 11 |
| Starting Page | 240 |
| e-ISSN | 17496632 |
| DOI | 10.1111/j.1749-6632.1998.tb08272.x |
| Journal | Annals of the New York Academy of Sciences |
| Issue Number | 1 CARDIAC |
| Volume Number | 853 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1998-09-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Annals of the New York Academy of Sciences Peripheral Vascular Disease Phosphorylation State Stimulation with Protein Kinase |
| Content Type | Text |
| Resource Type | Article |