Cardiac Hypertrophy Changes Compartmentation of cAMP in Non-Raft Membrane Microdomains
| Autor: | Kirstie A. De Jong, Viacheslav O. Nikolaev, Birgit Geertz, Nikoleta Pavlaki, Alexander Froese |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adenosine monophosphate endocrine system fluorescence resonance energy transfer Cardiomegaly 030204 cardiovascular system & hematology biosensor Article Mice 03 medical and health sciences chemistry.chemical_compound Membrane Microdomains 0302 clinical medicine cAMP compartmentation Cyclic AMP Animals Humans Receptor lcsh:QH301-705.5 Pressure overload Sarcolemma microdomain cardiac hypertrophy Lipid microdomain Phosphodiesterase General Medicine Raft Cell biology 030104 developmental biology lcsh:Biology (General) chemistry non-raft sarcolemma Second messenger system Female phosphodiesterase |
| Zdroj: | Cells, Vol 10, Iss 535, p 535 (2021) Cells Volume 10 Issue 3 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10030535 |
| Popis: | 3′,5′-Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger which plays critical roles in cardiac function and disease. In adult mouse ventricular myocytes (AMVMs), several distinct functionally relevant microdomains with tightly compartmentalized cAMP signaling have been described. At least two types of microdomains reside in AMVM plasma membrane which are associated with caveolin-rich raft and non-raft sarcolemma, each with distinct cAMP dynamics and their differential regulation by receptors and cAMP degrading enzymes phosphodiesterases (PDEs). However, it is still unclear how cardiac disease such as hypertrophy leading to heart failure affects cAMP signals specifically in the non-raft membrane microdomains. To answer this question, we generated a novel transgenic mouse line expressing a highly sensitive Förster resonance energy transfer (FRET)-based biosensor E1-CAAX targeted to non-lipid raft membrane microdomains of AMVMs and subjected these mice to pressure overload induced cardiac hypertrophy. We could detect specific changes in PDE3-dependent compartmentation of β-adrenergic receptor induced cAMP in non-raft membrane microdomains which were clearly different from those occurring in caveolin-rich sarcolemma. This indicates differential regulation and distinct responses of these membrane microdomains to cardiac remodeling. |
| Databáze: | OpenAIRE |
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