ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion
Experimental & Molecular Medicine
; : 820-827, 2007.
Article
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| WPRIM
| ID: wpr-62081
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WPRO
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.
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Assunto principal:
Fragmentos de Peptídeos
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Fosfato de Piridoxal
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Células Cultivadas
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Trifosfato de Adenosina
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Peptídeos beta-Amiloides
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Espécies Reativas de Oxigênio
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Ratos Sprague-Dawley
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Receptores Purinérgicos P2
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Microglia
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Comunicação Autócrina
Limite:
Animals
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2007
Tipo de documento:
Article