Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis

Int J Mol Sci

7 Aprile Apr 2022 one month ago
  • Banfi C, Amadio P, Zarà M, Brioschi M, Sandrini L, Barbieri SS

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 αIIbβ3 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.

Reference: Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis. Banfi C, Amadio P, Zarà M, Brioschi M, Sandrini L, Barbieri SS. Int J Mol Sci. 2022 Mar 4;23(5):2831.

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