Abstract
Present study demonstrated that fibrillar β-amyloid peptide (fAβ1-42) induced ATP release, which in turn activated NADPH oxidase via the P2X7 receptor (P2X7R). Reactive oxygen species (ROS) production in fAβ1-42-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 fAβ-stimulated microglia might be mediated by ATP released from the microglia. We therefore examined whether fAβ1-42-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 µM) or oxidized ATP (100 µM) inhibited fAβ-induced Ca2+ influx and reduced ROS generation to basal levels. Furthermore, ATP efflux from fAβ1-42-stimulated microglia was observed, and apyrase treatment decreased the generation of ROS. These findings provide conclusive evidence that fAβ-stimulated ROS generation in microglial cells is regulated by ATP released from the microglia in an autocrine manner.
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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Kim, S., Moon, J., Lee, H. et al. ATP released from β‐amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion. Exp Mol Med 39, 820–827 (2007). https://doi.org/10.1038/emm.2007.89
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DOI: https://doi.org/10.1038/emm.2007.89
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