KMID : 0620920070390060820
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Experimental & Molecular Medicine 2007 Volume.39 No. 6 p.820 ~ p.827
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ATP released from b-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion
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Kim Soo-Yoon
Moon Ju-Hyun Lee Hwan-Goo Kim Seung-Up Lee Yong-Beom
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Abstract
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Present study demonstrated that fibrillar b-amyloid peptide (fAb1-42) induced ATP release, which in turn activated NADPH oxidase via the P2X7 receptor (P2X7R). Reactive oxygen species (ROS) production in fAb1-42- 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 P2X7R in microglia, we hypothesized that ROS production in fAb-stimulated microglia might be mediated by ATP released from the microglia. We therefore examined whether fAb1-42-induced Ca2+ influx was mediated through P2X7R activation. In serial experiments, we found that microglial pretreatment with the P2X7R antagonists Pyridoxal-phosphate-6-azophenyl-2¡¯,4¡¯- disulfonate (100 mM) or oxidized ATP (100 mM) inhibited fAb-induced Ca2+ influx and reduced ROS generation to basal levels. Furthermore, ATP efflux from fAb1-42- stimulated microglia was observed, and apyrase treatment decreased the generation of ROS. These findings provide conclusive evidence that fAb-stimulated ROS generation in microglial cells is regulated by ATP released from the microglia in an autocrine manner.
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KEYWORD
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adenosine triphosphate, Alzheimer¡¯s disease, amyloid ¥â-protein, calcium, microglia, NADPH oxidase, purinoceptor P2Z, reactive oxygen species
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