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Globular adiponectin increases cGMP formation in blood platelets independently of nitric oxide

Aburima, A.; Naseem, K. M.; Riba, R.; Patel, B.; Aburima, Ahmed; Naseem, Khalid M.


A. Aburima

K. M. Naseem

R. Riba

B. Patel

Khalid M. Naseem


Background: Platelet-derived nitric oxide (NO) has been shown to play conflicting roles in platelet function, although it is accepted that NO mediates its actions through soluble guanylyl cyclase (sGC). This confusion concerning the roles of platelet NO may have arisen because of an uncharacterized mechanism for activation of sGC. Objectives: To examine the ability of the novel platelet agonist globular adiponectin (gAd) to stimulate the NO-independent cGMP-protein kinase G (PKG) signaling cascade. Methods: We used three independent markers of NO signaling, [ 3 H]l-citrulline production, cGMP accrual, and immunoblotting of vasodilator-stimulated phosphoprotein (VASP), to examine the NO signaling cascade in response to gAd. Results: gAd increased platelet cGMP formation, resulting in a dose- and time-dependent increase in phospho-VASP 157/239 . Phosphorylation of VASP in response to gAd was mediated by both protein kinase A and PKG. Importantly, cGMP formation occurred in the absence of NO synthase (NOS) activation and in the presence of NOS inhibitors. Indeed, inhibition of the NOS signaling cascade had no influence on gAd-mediated platelet aggregation. Exploration of the mechanism demonstrated that NO-independent cGMP formation, phosphorylation of VASP and association of sGCα 1 with heat shock protein-90 induced by gAd were blocked under conditions that inhibited Src kinases, implying a tyrosine kinase-dependent mechanism. Indeed, sGCα1 was reversibly tyrosine phosphorylated in response to gAd, collagen, and collagen-related peptide, an effect that required Src kinases and downstream Ca 2+ mobilization. Conclusions: These data demonstrate activation of the platelet cGMP signaling cascade by a novel tyrosine kinase-dependent mechanism in the absence of NO. © 2008 International Society on Thrombosis and Haemostasis.


Riba, R., Patel, B., Aburima, A., & Naseem, K. M. (2008). Globular adiponectin increases cGMP formation in blood platelets independently of nitric oxide. Journal of thrombosis and haemostasis : JTH, 6(12), 2121-2131.

Journal Article Type Article
Acceptance Date Aug 21, 2008
Online Publication Date Oct 1, 2008
Publication Date Nov 24, 2008
Journal J.Thromb.Haemost.
Print ISSN 1538-7933
Electronic ISSN 1538-7836
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 6
Issue 12
Pages 2121-2131
Keywords Adiponectin; analysis; Animals; biosynthesis; blood; Blood Platelets; Cattle; Cell Adhesion; Cell Adhesion Molecules; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Humans; Immunoblotting; metabolism; methods; Micr
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