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Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Mar 04; Vol. 23 (5). Date of Electronic Publication: 2022 Mar 04. - Publication Year :
- 2022
-
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 <subscript>3</subscript> injury of the carotid artery was delayed in Pcyox1 <superscript>-/-</superscript> mice, which were also protected from collagen/epinephrine induced thromboembolism. The Pcyox1 <superscript>-/-</superscript> 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 α <subscript>IIb</subscript> β <subscript>3</subscript> integrin activation in platelet-rich plasma, in response to adenosine diphosphate (ADP) or thrombin receptor agonist peptide (TRAP). Washed platelets from the Pcyox1 <superscript>-/-</superscript> and WT animals showed similar phosphorylation pathway activation, adhesion ability and aggregation. The presence of Pcyox1 <superscript>-/-</superscript> 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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35269975
- Full Text :
- https://doi.org/10.3390/ijms23052831