Inhibition of protein kinase A leads to cleavage of platelet GP I balpha and downregulation of GP I b-dependent platelet aggregation / 中华血液学杂志
Chinese Journal of Hematology
; (12): 171-174, 2009.
Article
em Zh
| WPRIM
| ID: wpr-314506
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To explore the regulatory role of protein kinase A (PKA) in platelet surface glycoprotein (GP) I balpha expression.</p><p><b>METHODS</b>Washed platelets from healthy volunteers were incubated with PKA inhibitor. The N-terminal fragment of GP I balpha (glycocalicin, GC) in the supernatant of platelet suspensions was detected by Western blot and GP I balpha surface expression by flow cytometry. Calpain activity was determined by cytoskeletal proteins proteolysis and calpain surface expression by flow cytometry. The effect of PKA inhibitor on ristocetin-induced platelet aggregation was measured by platelet aggregometer.</p><p><b>RESULTS</b>After PKA was inhibited in washed platelets, GP I balpha was cleaved and released to the supernatant, which significantly decreased the surface expression of GP I balpha (P < 0.05). The event was suppressed by pre-treatment with various calpain inhibitors, indicating that PKA inhibitor-mediated shedding was calpain dependent. The actin-binding protein (ABP) and talin proteolysis demonstrated that calpain was activated by PKA inhibitor and expressed on the platelet membrane. Ristocetin-induced aggregation was inhibited by PKA inhibitor.</p><p><b>CONCLUSION</b>PKA inhibition results in calpain-dependent GP I balpha shedding, which thus reduces GP I balpha surface expression and GP I balpha-dependent platelet aggregation. These results might provide a view to develop new drugs for thrombotic diseases.</p>
Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Farmacologia
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Plaquetas
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Inibidores da Agregação Plaquetária
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Calpaína
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Agregação Plaquetária
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Proteínas Quinases Dependentes de AMP Cíclico
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Complexo Glicoproteico GPIb-IX de Plaquetas
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Citometria de Fluxo
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Metabolismo
Limite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Hematology
Ano de publicação:
2009
Tipo de documento:
Article