Naslov
Developmental differences in platelet inhibition response to PGE1

Autori
Palma-Barqueros, Verónica ; Torregrosa, José Miguel ; Caparrós-Pérez, Eva ; Mota, Nerea ; Bohdan, Natalia ; Llanos, Maria del Carmen ; Jurak Begonja, Antonija ; Sola- Visner, Marta ; Vicente, Vicente ; Teruel-Montoya, Raul ; Rivera, Jose ; Ferrer Marin, Francisca

Izvornik
Neonatology (1661-7800) 117 (2020), 1; 15-23

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
neonatal platelets, prostaglandin E1, megakaryocytes

Sažetak
BACKGROUND: The mechanisms underlying neonatal platelets hyporesponsiveness are not fully understood. While previous studies have demonstrated developmental impairment of agonist-induced platelet activation, differences in inhibitory signaling pathways have been scarcely investigated. OBJECTIVE: To compare neonatal and adult platelets with regard to inhibition of platelet reactivity by prostaglandin E1 (PGE1). METHODS: Platelet-rich plasma from umbilical cord (CB) or adult blood was incubated with PGE1 (0-1 μM). We assessed aggregation in response to adenosine diphosphate (ADP), collagen, and thrombin receptor activating peptide as well as cyclic adenosine 3'5'-monophosphate (cAMP) levels (ELISA). Gαs, Gαi2, and total- and phospho- protein kinase A (PKA) were evaluated in adult and CB ultrapure and washed platelets, respectively, by immunoblotting. RESULTS: Neonatal (vs. adult) platelets display hypersensitivity to inhibition by PGE1 of platelet aggregation induced by ADP and collagen (PGE1 IC50: 14 and 117 nM for ADP and collagen, respectively, vs. 149 and 491 nM in adults). They also show increased basal and PGE1-induced cAMP levels. Mechanistically, PGE1 acts by binding to the prostanoid receptor IP (prostacyclin receptor), which couples to the Gαs protein-adenylate cyclase axis and increases intracellular levels of cAMP. cAMP activates PKA, which phosphorylates different target inhibitor proteins. Neonatal platelets showed higher basal and PGE1-induced cAMP levels, higher Gαs protein expression, and a trend to increased PKA-dependent protein phosphorylation compared to adult platelets. CONCLUSION: Neonatal platelets have a functionally increased PGE1- cAMP-PKA axis. This finding supports a downregulation of inhibitory when going from neonate to adult contributing to neonatal platelet hyporesponsiveness.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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