Serum ubiquitin via CXC chemokine receptor 4 triggered cyclooxygenase-1 ubiquitination possibly involved in the pathogenesis of aspirin resistance.
Clin Hemorheol Microcirc
; 61(1): 59-81, 2015.
Article
em En
| MEDLINE
| ID: mdl-25267459
ABSTRACT
Extracellular ubiquitin (Ub) with platelet aggregation property was found higher in acute myocardial infarction (AMI) patients. Here we detected the platelet functions and serum Ub levels in 250 AMI patients and 50 healthy volunteers before and after aspirin treatment. The influence of serum Ub on platelet functions was determined in vitro. We found that 47 out of 250 AMI patients showed aspirin resistance (AR) and 203 showed aspirin sensitivity (AS). During hospitalization, AR group had higher serum Ub levels than the AS group or the healthy group, and the serum Ub levels was related to the rates of thrombosis events. The patients with higher serum Ub levels showed that the platelets had more ubiquitinated platelets, higher contents of ubiquitinated proteins and ubiquitinated cyclooxygenase-1 (COX-1). The levels of ubiquitinated COX-1 in the platelets was inversely correlated with acetylated COX-1, the separated ubiquitinated COX-1 activity was approximately twofold or fourfold higher than the total COX-1(ubiquitinated COX-1 and COX-1) or COX-1. In vitro, we found that extracellular Ub, via the CXC chemokine receptor 4 (CXCR4) pathway, facilitated COX-1 to be ubiquitined and prevented aspirin to acetylate its target. Platelets had higher levels of ubiquitinated COX-1 showing poor response to aspirin. Such results were not detected in Ub-free serum or ovalbumin incubated platelets. Serum Ub, via the CXCR4 pathway, facilitated COX-1 to be ubiquitined and activated the platelets possibly involved in the pathogenesis of AR.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Plaquetária
/
Agregação Plaquetária
/
Aspirina
/
Receptores CXCR4
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Ubiquitina
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Ciclo-Oxigenase 1
/
Ubiquitinação
Tipo de estudo:
Etiology_studies
Limite:
Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Clin Hemorheol Microcirc
Assunto da revista:
ANGIOLOGIA
/
HEMATOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China