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Role of cGMP-PKG signaling in the protection of neonatal rat cardiac myocytes subjected to simulated ischemia/reoxygenation

Nitric oxide (NO) and B-type natriuretic peptide (BNP) are protective against ischemia–reperfusion injury as they increase intracellular cGMP level via activation of soluble (sGC) or particulate guanylate cyclases (pGC), respectively. The aim of the present study was to examine if the cGMP-elevating...

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Published in:Basic research in cardiology 2010-09, Vol.105 (5), p.643-650
Main Authors: Gorbe, Aniko, Giricz, Zoltan, Szunyog, Andrea, Csont, Tamas, Burley, Dwaine S., Baxter, Gary F., Ferdinandy, Peter
Format: Article
Language:English
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Summary:Nitric oxide (NO) and B-type natriuretic peptide (BNP) are protective against ischemia–reperfusion injury as they increase intracellular cGMP level via activation of soluble (sGC) or particulate guanylate cyclases (pGC), respectively. The aim of the present study was to examine if the cGMP-elevating mediators, NO and BNP, share a common downstream signaling pathway via cGMP-dependent protein kinase (PKG) in cardiac cytoprotection. Neonatal rat cardiac myocytes in vitro were subjected to 2.5 h simulated ischemia (SI) followed by 2 h reoxygenation. Cell viability was tested by trypan blue exclusion assay. PKG activity of cardiac myocytes was assessed by phospholamban (PLB) phosphorylation determined by western blot. Cell death was 34 ± 2% after SI/reoxygenation injury in the control group. cGMP-inducing agents significantly decreased irreversible cell injury: the cGMP analog 8-bromo-cGMP (8-Br-cGMP, 10 nM) decreased it to 13 ± 1% ( p  
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-010-0097-0