Congress of the International Society on Thrombosis and Haemostasis

Differential roles of cAMP and cGMP in megakaryocyte maturation and platelet formation

Abstract number: PP-WE-077

Jurak Begonja¹ A., Gambaryan² S., Schulze³ H., Patel Hett¹ S., Italiano¹ J.E., Hartwig¹ J.H., Walter² U.

¹¹Translational Medicine, BWH and HMS, Boston, USA ²²Institute of Clinical Biochemistry and Pathobiochemistry, Wuerzburg ³³Department of Pediatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany

How-to-cite Jurak Begonja A, Gambaryan S, Schulze H, Patel Hett S, Italiano JE, Hartwig JH, Walter U. Differential roles of cAMP and cGMP in megakaryocyte maturation and platelet formation. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-WE-077

Platelets are released by megakaryocytes through long cytoplasmic extensions called proplatelets. Here we show that megakaryocyte development from mouse fetal liver cells is accompanied with a dramatic increase in cAMP levels, as well as increase in expression of proteins involved in cAMP/cGMP signaling (sGC, PKG, PKA, VASP, MENA). The cyclic nucleotides cGMP and cAMP are important inhibitory signaling molecules in platelets. Formation of cGMP and cAMP in platelets is stimulated by endothelial-derived NO and prostacyclin (PGI2), which then mediates inhibition of platelets by activating protein kinase G (PKG) and protein kinase A (PKA). In contrast, cGMP levels increase during early megakaryocyte development but drop to basal levels as megakaryocytes mature due to an increased expression of PDE5, which hydrolyses cGMP. Stimulation of the PGE receptor/adenylyl cyclase or sGC/PKG increased the phosphorylation of VASP in megakaryocytes, indicating functional signalling systems. Down regulation of cAMP/PKA signaling decreased megakaryocyte number and ploidy, while down regulation of cGMP/PKG was without effect. In the final step of megakaryocyte maturation, including platelet release, cGMP and cAMP had mild but opposing effects: cGMP increased platelet production while cAMP decreased it. These results show that cAMP/cGMP signaling, in addition to inhibiting platelet activation, is also involved in megakaryocyte and platelet development.

Disclosure of interest: none declared.

To cite this abstract use the following format:

Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number

Session Details

Date:	Unpresented
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Session name:	ISTH2009
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