Document Detail

Activation of caspases-9, -3 and -8 in human platelets triggered by BH3-only mimetic ABT-737 and calcium ionophore A23187: caspase-8 is activated via bypass of the death receptors.
MedLine Citation:
PMID:  23025479     Owner:  NLM     Status:  Publisher    
Platelet apoptosis and activation have been studied in human platelets treated with BH3-only mimetic ABT-737 and calcium ionophore A23187, agents triggering apoptosis through the intrinsic mitochondrial pathway. Platelet apoptosis was determined as activation of crucial apoptosis-associated caspases, initiator caspase-9 of intrinsic apoptosis pathway, executioner caspase-3 and initiator caspase-8 of extrinsic death receptor pathway, and platelet activation was detected by P-selectin (CD62) exposure on the platelet surface. We found that ABT-737 predominantly induced activation of caspases-9, -3 and -8 rather than CD62 exposure, whereas A23187 induces both caspases activation and CD62 exposure. Caspase-8 activation was stimulated independently of the extrinsic apoptosis pathway via mitochondrial membrane permeabilization and depolarization. These data suggest that (i) caspase-8 activation is triggered in ABT-737- and A23187-treated anucleate platelets through the mitochondria-initiated caspase activation cascade bypassing the death receptors, and (ii) ABT-737-treated platelets are a useful experimental tool for discerning the role of platelet apoptosis in platelet function and survival.
Asuman Mutlu; Armen V Gyulkhandanyan; John Freedman; Valery Leytin
Related Documents :
16684969 - Phospholipase a2-generated lipid mediators in the brain: the good, the bad, and the ugly.
8129489 - Are events after endotoxemia related to circulating phospholipase a2?
7639679 - Aggretin, a novel platelet-aggregation inducer from snake (calloselasma rhodostoma) ven...
17456899 - The transfer of vldl-associated phospholipids to activated platelets depends upon cytos...
1889959 - Influence of 4-hydroxynonenal on bombesin-induced stimulation of phospholipase c activi...
2841909 - Prostaglandins, leukotrienes, phospholipase, platelet activating factor, and cytokines:...
2166499 - Studies on the mechanism of platelet-activating factor production in gm-csf primed neut...
21740339 - Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-...
22994699 - High on-treatment platelet reactivity on commonly prescribed antiplatelet agents follow...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  British journal of haematology     Volume:  -     ISSN:  1365-2141     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Division of Transfusion Medicine, Department of Laboratory Medicine, The Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Mitogenomics reveals two subspecies in Coelomactra antiquata (Mollusca: Bivalvia).
Next Document:  Synthetic route for supported gold nanoparticles Layered Double Hydroxides as efficient catalysts to...