期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms23052831
关键词
Prenylcysteine Oxidase 1; thrombosis; platelets
资金
- Italian Ministry of Health, Italy [2755301 MPP 1A, 2757640MPP 2B, RF-2013-02355543]
The absence of PCYOX1 leads to platelet hypo-reactivity and impaired arterial thrombosis, suggesting PCYOX1 as a potential novel target for antithrombotic drugs.
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 alpha(IIb)beta(3) 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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