Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis.
Int J Mol Sci
; 23(5)2022 Mar 04.
Article
en En
| MEDLINE
| ID: mdl-35269975
ABSTRACT
Prenylcysteine Oxidase 1 (PCYOX1) is an enzyme involved in the degradation of prenylated proteins. It is expressed in different tissues including vascular and blood cells. We recently showed that the secretome from Pcyox1-silenced cells reduced platelet adhesion both to fibrinogen and endothelial cells, suggesting a potential contribution of PCYOX1 into thrombus formation. Here, we show that in vivo thrombus formation after FeCl3 injury of the carotid artery was delayed in Pcyox1-/- mice, which were also protected from collagen/epinephrine induced thromboembolism. The Pcyox1-/- mice displayed normal blood cells count, vascular procoagulant activity and plasma fibrinogen levels. Deletion of Pcyox1 reduced the platelet/leukocyte aggregates in whole blood, as well as the platelet aggregation, the alpha granules release, and the αIIbß3 integrin activation in platelet-rich plasma, in response to adenosine diphosphate (ADP) or thrombin receptor agonist peptide (TRAP). Washed platelets from the Pcyox1-/- and WT animals showed similar phosphorylation pathway activation, adhesion ability and aggregation. The presence of Pcyox1-/- plasma impaired agonist-induced WT platelet aggregation. Our findings show that the absence of PCYOX1 results in platelet hypo-reactivity and impaired arterial thrombosis, and indicates that PCYOX1 could be a novel target for antithrombotic drugs.
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Bases de datos:
MEDLINE
Asunto principal:
Liasas de Carbono-Azufre
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Trombosis
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Células Endoteliales
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia