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Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
cAMP regulates ADP-induced HSP27 phosphorylation in human platelets
Yukiko Enomoto1, Seiji Adachi, Tomoaki Doi
1Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
International Journal of Molecular Medicine
|March 5, 2011
Summary
Elevated cyclic adenosine monophosphate (cAMP) inhibits platelet activation by suppressing heat shock protein 27 (HSP27) phosphorylation via p38 MAP kinase. This finding reveals a novel mechanism regulating platelet function.
Area of Science:
- Biochemistry
- Molecular Biology
- Hematology
Background:
- Platelet activation is crucial for hemostasis but also implicated in thrombosis.
- Cyclic adenosine monophosphate (cAMP) is known to inhibit platelet aggregation and other functions.
- Previous work linked adenosine diphosphate (ADP)-induced heat shock protein 27 (HSP27) phosphorylation via p38 MAP kinase to platelet-derived growth factor (PDGF)-AB secretion and soluble CD40 ligand (sCD40L) release.
Purpose of the Study:
- To investigate the regulatory role of cAMP in adenosine diphosphate (ADP)-stimulated platelet activation.
- To determine the relationship between cAMP levels and the phosphorylation of heat shock protein 27 (HSP27) in platelets.
- To elucidate the impact of cAMP on ADP-induced p38 MAP kinase activity and downstream signaling.
Main Methods:
- Platelet activation induced by adenosine diphosphate (ADP).
- Treatment with 8-bromoadenosine-3',5'-cyclic monophosphate (8-bromo-cAMP), a cAMP analogue, or cilostazol, a phosphodiesterase inhibitor.
- Assessment of p38 MAP kinase phosphorylation levels.
- Measurement of heat shock protein 27 (HSP27) phosphorylation.
- Quantification of platelet-derived growth factor (PDGF)-AB secretion and soluble CD40 ligand (sCD40L) release.
Main Results:
- 8-bromo-cAMP and cilostazol significantly attenuated ADP-induced p38 MAP kinase phosphorylation.
- Both agents suppressed ADP-induced HSP27 phosphorylation.
- Elevated cAMP levels, induced by 8-bromo-cAMP, forskolin, or cilostazol, markedly reduced ADP-stimulated PDGF-AB secretion and sCD40L release.
Conclusions:
- Cyclic adenosine monophosphate (cAMP) plays a suppressive role in adenosine diphosphate (ADP)-stimulated platelet activation.
- cAMP inhibits platelet activation by suppressing HSP27 phosphorylation through the p38 MAP kinase pathway.
- These findings provide new insights into the molecular mechanisms governing platelet function and potential therapeutic targets.
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