| Shen MY |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=2.376 ------>paper_class3=2 ------>paper_class2=1 ------>vol=588 ------>confirm_bywho=thfong ------>insert_bywho=thfong ------>Jurnal_Rank=40.5 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=266 ------>medlineContent= ------>unit=E0107 ------>insert_date=20080611 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=European Journal of Pharmacology ------>paper_name=Amyloid beta peptide-activated signal pathways in human platelets ------>confirm_date=20081115 ------>tch_id=088001 ------>pmid=18511035 ------>page1=259 ------>fullAbstract=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. ------>tmu_sno=None ------>sno=18693 ------>authors2=Hsiao G ------>authors3=Fong TH ------>authors4=Chen HM ------>authors5=Chou DS ------>authors6=Lin CH, Sheu JR, Hsu CY ------>authors6_c= ------>authors=Shen MY ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Amyloid beta peptide-activated signal pathways in human platelets. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=7 |