PDE2 at the crossway between cAMP and cGMP signalling in the heart
| Autor: | Michael Wagner, Miriam Zeller, Silvio Weber, Frank Wunder, Kaomei Guan, Ali El-Armouche |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Phosphodiesterase Inhibitors Phosphodiesterase 3 Biology 03 medical and health sciences Cyclic nucleotide chemistry.chemical_compound Cyclic AMP Animals Humans Molecular Targeted Therapy Cyclic GMP Phosphoric Diester Hydrolases Kinase Effector Myocardium Phosphodiesterase Cell Biology Cell biology Crosstalk (biology) 030104 developmental biology chemistry Biochemistry Second messenger system PDE10A Signal Transduction |
| Zdroj: | Cellular Signalling. 38:76-84 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2017.06.020 |
| Popis: | The cyclic nucleotides cAMP and cGMP are central second messengers in cardiac cells and critical regulators of cardiac physiology as well as pathophysiology. Consequently, subcellular compartmentalization allows for spatiotemporal control of cAMP/cGMP metabolism and subsequent regulation of their respective effector kinases PKA or PKG is most important for cardiac function in health and disease. While acute cAMP-mediated signalling is a mandatory prerequisite for the physiological fight-or-flight response, sustained activation of this pathway may lead to the progression of heart failure. In contrast, acute as well as sustained cGMP-mediated signalling can foster beneficial features, e.g. anti-hypertrophic and vasodilatory effects. These two signalling pathways seem to be intuitively counteracting and there is increasing evidence for a functionally relevant crosstalk between cAMP and cGMP signalling pathways on the level of cyclic nucleotide hydrolysing phosphodiesterases (PDEs). Among this diverse group of enzymes, PDE2 may fulfill a unique integrator role. Equipped with dual substrate specificity for cAMP as well as for cGMP, it is the only cAMP hydrolysing PDE, which is allosterically activated by cGMP. Recent studies have revealed strongly remodelled cAMP/cGMP microdomains and subcellular concentration profiles in different cardiac pathologies, leading to a putatively enhanced involvement of PDE2 in cAMP/cGMP breakdown and crosstalk compared to the other cardiac PDEs. This review sums up the current knowledge about molecular properties and regulation of PDE2 and explains the complex signalling network encompassing PDE2 in order to better understand the functional role of PDE2 in distinct cell types in cardiac health and disease. Moreover, this review gives an outlook in which way PDE2 may serve as a therapeutic target to treat cardiac disease. |
| Databáze: | OpenAIRE |
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