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
in Chinese
| WPRIM
| ID: wpr-314506
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>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Blood Platelets
/
Platelet Aggregation Inhibitors
/
Calpain
/
Platelet Aggregation
/
Cyclic AMP-Dependent Protein Kinases
/
Platelet Glycoprotein GPIb-IX Complex
/
Flow Cytometry
/
Metabolism
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Hematology
Year:
2009
Type:
Article
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