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ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion
Experimental & Molecular Medicine ; : 820-827, 2007.
Artigo em Inglês | 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.
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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fragmentos de Peptídeos / Fosfato de Piridoxal / Células Cultivadas / Trifosfato de Adenosina / Peptídeos beta-Amiloides / Espécies Reativas de Oxigênio / Ratos Sprague-Dawley / Receptores Purinérgicos P2 / Microglia / Comunicação Autócrina Limite: Animais Idioma: Inglês Revista: Experimental & Molecular Medicine Ano de publicação: 2007 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fragmentos de Peptídeos / Fosfato de Piridoxal / Células Cultivadas / Trifosfato de Adenosina / Peptídeos beta-Amiloides / Espécies Reativas de Oxigênio / Ratos Sprague-Dawley / Receptores Purinérgicos P2 / Microglia / Comunicação Autócrina Limite: Animais Idioma: Inglês Revista: Experimental & Molecular Medicine Ano de publicação: 2007 Tipo de documento: Artigo