scholarly journals Lipopolysaccharide Stimulates Platelet Secretion and Potentiates Platelet Aggregation via TLR4/MyD88 and the cGMP-Dependent Protein Kinase Pathway

2009 ◽  
Vol 182 (12) ◽  
pp. 7997-8004 ◽  
Author(s):  
Guoying Zhang ◽  
Jingyan Han ◽  
Emily J. Welch ◽  
Richard D. Ye ◽  
Tatyana A. Voyno-Yasenetskaya ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Protein Kinase ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Kinase Pathway ◽  
Platelet Secretion

LPS Stimulates Platelet Secretion and Promotes Platelet Aggregation Via TLR4/MyD88 and the cGMP-Dependent Protein Kinase Pathway.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3658-3658
Author(s):  
Guoying Zhang ◽  
Emily Welch ◽  
Asrar B. Malik ◽  
Xiaoping Du ◽  
Zhenyu Li
Keyword(s):  
Platelet Aggregation ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Critical Role ◽  
Atp Release ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Platelet Secretion

Abstract Bacterial lipopolysaccharide (LPS) induces rapid thrombocytopenia, hypotension and sepsis. Although growing evidence suggests that platelet activation plays a critical role in LPS-induced thrombocytopenia and tissue damage, the mechanism of LPS-mediated platelet activation is unclear. Here we show that LPS stimulated platelet secretion of dense and alpha granules as indicated by ATP release and P-selectin expression, and thus enhanced platelet activation induced by low concentrations of platelet agonists. Platelets express components of the LPS receptor-signaling complex, including Toll-like receptor (TLR4), CD14, MD2, and MyD88. The effect of LPS on platelet activation was abolished by an anti-TLR4 blocking antibody or TLR4 knockout. Furthermore, LPS-induced potentiation of platelet aggregation and FeCl3-induced thrombus formation were abolished in MyD88 knockout mice. Importantly, TLR4 mediates LPS-induced cGMP elevation and the stimulatory effect of LPS on platelet aggregation was also abolished by inhibitors of nitric oxide synthase (NOS) and the cGMP-dependent protein kinase (PKG). Thus, LPS promotes platelet secretion and aggregation through a TLR4/MyD88 and cGMP/PKG-dependent pathway.

AKT Mediates Platelet Activation by Stimulating Nitric Oxide Synthesis and cGMP Elevation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1652-1652
Author(s):  
Aleksandra Stojanovic ◽  
Jasna A. Marjanovic ◽  
Viktor Brokovych ◽  
Randal A. Skidgel ◽  
Nissim Hay ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Critical Role ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Low Concentrations ◽  
Cgmp Pathway ◽  
Dependent Protein ◽  
Platelet Secretion

Abstract Phosphoinositide 3-kinase (PI3-K) and Akt play important roles in platelet activation. However, the downstream mechanisms for their roles are unclear. We have recently shown that nitric oxide (NO) synthase 3 (NOS3) and cGMP-dependent protein kinase stimulate platelet secretion and aggregation. Here we show that PI3-K-mediated Akt activation plays a critical role in agonist-stimulated platelet NO synthesis and cGMP elevation. Agonist-induced elevation of NO and cGMP was inhibited by Akt inhibitors and reduced in Akt-1 knockout platelets. Akt-1 knockout or Akt inhibitor-treated platelets showed reduced platelet secretion and aggregation in response to low concentrations of agonists, which can be reversed by low concentrations of sodium nitroprusside (SNP) or cGMP analogs. Similarly, PI3-K inhibitors diminished elevation of cGMP and also inhibited platelet secretion and the second-wave platelet aggregation, which was also partially reversed by cGMP analogs and by SNP. These results indicate that the NO-cGMP pathway is an important downstream mechanism mediating PI3-K and Akt signals leading to platelet secretion and aggregation. Conversely, the PI3-K-Akt pathway is a major upstream mechanism responsible for activating the NO-cGMP pathway. Thus, this study delineates a novel platelet activation pathway involving sequential activation of PI3-K, Akt, NOS3, sGC, and cGMP-dependent protein kinase.

scholarly journals A Platelet Secretion Pathway Mediated by cGMP-dependent Protein Kinase

2004 ◽  
Vol 279 (41) ◽  
pp. 42469-42475 ◽  
Author(s):  
Zhenyu Li ◽  
Guoying Zhang ◽  
Jasna Ajdic Marjanovic ◽  
Changgeng Ruan ◽  
Xiaoping Du
Keyword(s):  
Protein Kinase ◽  
Dependent Protein Kinase ◽  
Secretion Pathway ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Platelet Secretion
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