Thrombin induces apoptotic events through the generation of reactive oxygen species in human platelets.
J Thromb Haemost
; 5(6): 1283-91, 2007 Jun.
Article
em En
| MEDLINE
| ID: mdl-17567446
ABSTRACT
BACKGROUND:
Thrombin is a major physiological platelet agonist that activates a number of cell functions including aggregation. Platelet stimulation with thrombin has been shown to result in the development of apoptotic events, including activation of caspases-3 and -9, cytochrome c release and phosphatidylserine (PS) exposure; however, the mechanism underlying the activation of apoptosis remains unclear.OBJECTIVES:
In the present study, we aim to investigate whether endogenously generated reactive oxygen species upon thrombin stimulation is required for the activation of apoptosis in human platelets.METHODS:
Changes in the mitochondrial membrane potential were registered using the dye JC-1; caspase-3 and -9 activity was determined from the cleavage of their respective specific fluorogenic substrates; PS externalization was estimated using annexin V-fluorescein isothicyanate and cytochrome c release was detected by Western blotting in samples from the mitochondrial and cytosolic fractions.RESULTS:
Treatment of platelets with thrombin stimulates mitochondrial membrane potential depolarization and endogenous generation of H(2)O(2) . Platelet exposure to exogenous H(2)O(2) results in cytochrome c release and activation of caspases-9. In addition, H(2)O(2) induces the activation of caspase-3 and PS exposure by a mechanism dependent on cytochrome c release and caspase-9 activation. Finally, thrombin-evoked development of apoptotic events was impaired by treatment with catalase.CONCLUSION:
Our results indicate that thrombin-induced apoptosis is likely mediated by endogenous generation of H(2)O(2) in human platelets.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Trombina
/
Espécies Reativas de Oxigênio
/
Apoptose
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article