Effects and regulation of inhibitor-1 in the heart and its therapeutic potential in heart failure
Principal investigators:Ali El-Armouche and Thomas Eschenhagen,
Institute of Experimental and Clinical Pharmacology and Toxicology, UKE
Co-workers partly involved:Ariane Schmechel
Katrin Wittköpper
Jutta Starbatty
Franziska Degenhardt
Fabian Gocht
Florian Weinberger
Christiane Neuber
Sandra Burdock
Contact:
a.el-armouche@uke.uni-hamburg.de
Objectives
- I-1 and compartmentation of PKA-effects (e.g. PLB vs. RyR)
- Consequences of manipulating WT I-1 and mutated I-1 levels in vivo
- Methodological improvement of I-1 immunological detection
- I-1´s regulation by phosphatases in healthy and “diseased” CMs
- I-1´s role in reverse remodeling after β-blocker treatment
Selected references
- El-Armouche A, Rau T, Zolk O, Ditz D, Pamminger T, Zimmermann W-H, Jäckel E, Harding SE, Boknik P, Neumann J, Eschenhagen T. Evidence for protein phosphatase inhibitor-1 playing an amplifier role in β-adrenergic signaling. FASEB J 2003;17:437-439
- Wiechert S, EI-Armouche A, Rau T, Zimmermann W-H, Eschenhagen T. 24-h Langendorff-perfused neonatal rat heart to study the impact of adenoviral gene transfer. Am J Physiol Heart Circ Physiol 2003;285:907-914
- El-Armouche A, Rau T, Zolk O, Eschenhagen T. Role of inhibitory G-protein α2 in heart failure. Cardiovasc Res 2003;60:478-87
- Zolk O, Marx M, Jäckel E, El-Armouche A, Eschenhagen T. β-Adrenergic stimulation induces cardiac ankyrin repeat protein expression: Involvement of protein kinase A and calmodulin-dependent kinase. Cardiovasc Res 2003;59:563-572
- El-Armouche A, Pamminger T, Ditz D, Zolk O, Eschenhagen T. Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts. Cardiovasc Res 2004;6:87-93
- El-Armouche A, Jäckel E, Boheler KR, Boknik P, Hertle B, Neumann J, Eschenhagen T. Ouabain treatment is associated with upregulation of phosphatase inhibitor-1 and Na+/Ca(2+)-exchanger and β-adrenergic sensitization in rat hearts. Biochem Biophys Res Commun 2004;318:219-226
