ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion
Experimental & Molecular Medicine
;
: 820-827, 2007.
Artículo
en Inglés
| WPRIM
| ID: wpr-62081
ABSTRACT
Present study demonstrated that fibrillar beta-amyloid peptide (fAbeta(1-42)) induced ATP release, which in turn activated NADPH oxidase via the P2X(7) receptor (P2X(7)R). Reactive oxygen species (ROS) production in fAbeta(1-42)-treated microglia appeared to require Ca2+ influx from extracellular sources, because ROS generation was abolished to control levels in the absence of extracellular Ca2+. Considering previous observation of superoxide generation by Ca2+ influx through P2X(7)R in microglia, we hypothesized that ROS production in fAbeta-stimulated microglia might be mediated by ATP released from the microglia. We therefore examined whether fAbeta(1-42)-induced Ca2+ influx was mediated through P2X(7)R activation. In serial experiments, we found that microglial pretreatment with the P2X(7)R antagonists Pyridoxal-phosphate-6-azophenyl-2',4'- disulfonate (100 micrometer) or oxidized ATP (100 micrometer) inhibited fAbeta-induced Ca2+ influx and reduced ROS generation to basal levels. Furthermore, ATP efflux from fAbeta(1-42)-stimulated microglia was observed, and apyrase treatment decreased the generation of ROS. These findings provide conclusive evidence that fAbeta-stimulated ROS generation in microglial cells is regulated by ATP released from the microglia in an autocrine manner.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fragmentos de Péptidos
/
Fosfato de Piridoxal
/
Células Cultivadas
/
Adenosina Trifosfato
/
Péptidos beta-Amiloides
/
Especies Reactivas de Oxígeno
/
Ratas Sprague-Dawley
/
Receptores Purinérgicos P2
/
Microglía
/
Comunicación Autocrina
Límite:
Animales
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2007
Tipo del documento:
Artículo
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