Source:http://linkedlifedata.com/resource/pubmed/id/18511035
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2-3
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| pubmed:dateCreated |
2008-6-16
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| pubmed:abstractText |
Amyloid beta peptide (amyloid-beta), which accumulates in the cerebral microvessels in an age-dependent manner, plays a key role in the pathogenesis of cerebral amyloid angiopathy. Platelets are an important cellular element in vasculopathy of various causes. Amyloid-beta may activate or potentiate platelet aggregation. The present study explored the signaling events that underlie amyloid-beta activation of platelet aggregation. Platelet aggregometry, immunoblotting and assays to detect activated cellular events were applied to examine the signaling processes of amyloid-beta activation of platelets. Exogenous amyloid-beta (1-2 microM) potentiated platelet aggregation caused by collagen and other agonists. At higher concentrations (5-10 microM), amyloid-beta induced platelet aggregation which was accompanied by an increase in thromboxane A2 (TxA2) formation. These amyloid-beta actions on platelets were causally related to amyloid-beta activation of p38 mitogen-activated protein kinase (MAPK). Inhibitors of p38 MAPK and its upstream signaling pathways including proteinase-activated receptor 1 (PAR1), Ras, phosphoinositide 3-kinase (PI3-kinase), or Akt, but not extracellular signal-regulated kinase 2 (ERK2)/c-Jun N-terminal kinase 1 (JNK1), blocked amyloid-beta-induced platelet activation. These findings suggest that the p38 MAPK, but not ERK2 or JNK1 pathway, is specifically activated in amyloid-beta-induced platelet aggregation with the following signaling pathway: PAR1 --> Ras/Raf --> PI3-kinase --> Akt --> p38 MAPK --> cytosolic phospholipase A2 (cPLA2)--> TxA2. In conclusion, this study demonstrates amyloid-beta activation of a p38 MAPK signaling pathway in platelets leading to aggregation. Further studies are needed to define the specific role of amyloid-beta activation of platelets in the pathogenesis of vasculopathy including cerebral amyloid angiopathy.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 8,
http://linkedlifedata.com/resource/pubmed/chemical/N3-cyclopropyl-7-((4-(1-methylethyl)...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-2,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0014-2999
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
7
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| pubmed:volume |
588
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
259-66
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:18511035-Amyloid beta-Peptides,
pubmed-meshheading:18511035-Blood Platelets,
pubmed-meshheading:18511035-Enzyme Activation,
pubmed-meshheading:18511035-Humans,
pubmed-meshheading:18511035-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:18511035-Mitogen-Activated Protein Kinase 8,
pubmed-meshheading:18511035-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18511035-Phosphorylation,
pubmed-meshheading:18511035-Platelet Aggregation,
pubmed-meshheading:18511035-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18511035-Pyrroles,
pubmed-meshheading:18511035-Quinazolines,
pubmed-meshheading:18511035-Receptor, PAR-1,
pubmed-meshheading:18511035-Receptor, PAR-2,
pubmed-meshheading:18511035-Signal Transduction,
pubmed-meshheading:18511035-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2008
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| pubmed:articleTitle |
Amyloid beta peptide-activated signal pathways in human platelets.
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| pubmed:affiliation |
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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