Using direct injection mass spectrometry (DIMS) we discovered that deoxyribose-1-phosphate (dRP) is released by platelets upon activation. Interestingly, the addition of exogenous dRP to human platelets significantly increased platelet aggregation and integrin αIIbβ3 activation in response to thrombin. In parallel, genetically modified platelets with double genetic deletion of thymidine phosphorylase and uridine phosphorylase were characterised by reduced release of dRP, impaired aggregation and decreased integrin αIIbβ3 activation in response to thrombin. In vitro platelet adhesion onto fibrinogen and collagen under physiological flow conditions was potentiated by treatment of human platelets with exogenous dRP and impaired in transgenic platelets with reduced dRP release. Human and mouse platelets responded to dRP treatment with a sizeable increase in reactive oxygen species (ROS) generation and the pre-treament with the antioxidant apocynin abolished the effect of dRP on aggregation and integrin activation. Experiments directly assessing the activation of the small G protein Rap1b and protein kinase C suggested that dRP increases the basal levels of activity of these two pivotal platelet-activating pathways in a redox-dependent manner. Taken together, we present evidence that dRP is a novel autocrine amplifier of platelet activity, which acts on platelet redox levels and modulates integrin αIIbβ3.

Vara, D.s., Campanella, M., Canobbio, I., Dunn, W.b., Pizzorno, G., Hirano, M., et al. (2013). Autocrine amplification of integrin αIIbβ3 activation and platelet adhesive responses by deoxyribose-1-phosphate. THROMBOSIS AND HAEMOSTASIS, 109(6), 1108-1119 [10.1160/TH12-10-0751].

Autocrine amplification of integrin αIIbβ3 activation and platelet adhesive responses by deoxyribose-1-phosphate

Campanella, Michelangelo
;
2013-06-01

Abstract

Using direct injection mass spectrometry (DIMS) we discovered that deoxyribose-1-phosphate (dRP) is released by platelets upon activation. Interestingly, the addition of exogenous dRP to human platelets significantly increased platelet aggregation and integrin αIIbβ3 activation in response to thrombin. In parallel, genetically modified platelets with double genetic deletion of thymidine phosphorylase and uridine phosphorylase were characterised by reduced release of dRP, impaired aggregation and decreased integrin αIIbβ3 activation in response to thrombin. In vitro platelet adhesion onto fibrinogen and collagen under physiological flow conditions was potentiated by treatment of human platelets with exogenous dRP and impaired in transgenic platelets with reduced dRP release. Human and mouse platelets responded to dRP treatment with a sizeable increase in reactive oxygen species (ROS) generation and the pre-treament with the antioxidant apocynin abolished the effect of dRP on aggregation and integrin activation. Experiments directly assessing the activation of the small G protein Rap1b and protein kinase C suggested that dRP increases the basal levels of activity of these two pivotal platelet-activating pathways in a redox-dependent manner. Taken together, we present evidence that dRP is a novel autocrine amplifier of platelet activity, which acts on platelet redox levels and modulates integrin αIIbβ3.
giu-2013
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Animals
Blood Platelets
Flow Cytometry
Humans
Mass Spectrometry
Mice
Mice, Inbred C57BL
Oxidation-Reduction
Platelet Activation
Platelet Glycoprotein GPIIb-IIIa Complex
Protein Kinase C
Reactive Oxygen Species
Ribosemonophosphates
Signal Transduction
Thrombin
Thymidine Phosphorylase
Uridine Phosphorylase
rap GTP-Binding Proteins
Platelet Adhesiveness
Vara, D.s., Campanella, M., Canobbio, I., Dunn, W.b., Pizzorno, G., Hirano, M., et al. (2013). Autocrine amplification of integrin αIIbβ3 activation and platelet adhesive responses by deoxyribose-1-phosphate. THROMBOSIS AND HAEMOSTASIS, 109(6), 1108-1119 [10.1160/TH12-10-0751].
Vara, Ds; Campanella, M; Canobbio, I; Dunn, Wb; Pizzorno, G; Hirano, M; Pula, G
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/265719
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact