Ca2+/calmodulin‐dependent protein kinase IIδ orchestrates G‐protein‐coupled receptor and electric field stimulation‐induced cardiomyocyte hypertrophy
W Zhang, F Qi, DQ Chen, WY Xiao… - Clinical and …, 2010 - Wiley Online Library
W Zhang, F Qi, DQ Chen, WY Xiao, J Wang, WZ Zhu
Clinical and Experimental Pharmacology and Physiology, 2010•Wiley Online LibraryG‐Protein‐coupled receptors (GPCR) and electrical field stimulation (EFS) regulate cardiac
function and pathological remodelling, including cardiac hypertrophy. Cardiac
Ca2+/calmodulin‐dependent protein kinase (CaMK) IIδ expression and activity are altered
in cardiac hypertrophy and heart failure. The aim of the present study was to determine the
effects of CaMKIIδ isoforms on neonatal rat cardiomyocyte hypertrophy induced by GPCR
and EFS. 2. Cardiac hypertrophy was induced by angiotensin II, phenylephrine or EFS and …
function and pathological remodelling, including cardiac hypertrophy. Cardiac
Ca2+/calmodulin‐dependent protein kinase (CaMK) IIδ expression and activity are altered
in cardiac hypertrophy and heart failure. The aim of the present study was to determine the
effects of CaMKIIδ isoforms on neonatal rat cardiomyocyte hypertrophy induced by GPCR
and EFS. 2. Cardiac hypertrophy was induced by angiotensin II, phenylephrine or EFS and …
Summary
1. G‐Protein‐coupled receptors (GPCR) and electrical field stimulation (EFS) regulate cardiac function and pathological remodelling, including cardiac hypertrophy. Cardiac Ca2+/calmodulin‐dependent protein kinase (CaMK) IIδ expression and activity are altered in cardiac hypertrophy and heart failure. The aim of the present study was to determine the effects of CaMKIIδ isoforms on neonatal rat cardiomyocyte hypertrophy induced by GPCR and EFS.
2. Cardiac hypertrophy was induced by angiotensin II, phenylephrine or EFS and was confirmed by increases in cell volume, [3H]‐leucine incorporation, sarcomere assembly and mRNA expression of atrial natriuretic factor and β‐myosin heavy chain. The effects of the CaMKII inhibitors KN93 and autocamtide 2‐related inhibitory peptide (AIP) on cardiomyocyte hypertrophy were investigated, as was the effect of overexpression of dominate negative CaMKIIδ.
3. Cardiomyocyte hypertrophy was inhibited by the CaMKII inhibitors KN93 and AIP and by overexpression of dominate negative CaMKIIδ, but was potentiated by overexpression of wild‐type CaMKIIδB or CaMKIIδC. Activation of CaMKII by GPCR agonists or EFS was inhibited by the CaMKII inhibitors.
4. The GPCR agonists and EFS synergistically activated CaMKII and upregulated CaMKIIδB and CaMKIIδC mRNA expression and protein synthesis. All these effects were abolished by the CaMKII inhibitors.
5. The findings of the present study indicate that CaMKII orchestrates additive prohypertrophic factors between GPCR agonists and EFS. Thus, CaMKII may be a useful target in the clinical treatment of hypertrophy and cardiac remodelling.
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