1. Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis.
- Author
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Banfi C, Amadio P, Zarà M, Brioschi M, Sandrini L, and Barbieri SS
- Subjects
- Animals, Blood Platelets metabolism, Cysteine analogs & derivatives, Fibrinogen metabolism, Mice, Oxidoreductases metabolism, Platelet Activation, Platelet Aggregation, Platelet Glycoprotein GPIIb-IIIa Complex metabolism, Carbon-Sulfur Lyases metabolism, Endothelial Cells metabolism, Thrombosis metabolism
- 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 FeCl
3 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 αIIb β3 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.- Published
- 2022
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