title: ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion.
abstract: Present study demonstrated that fibrillar beta-amyloid peptide (fAbeta1-42) induced ATP release, which in turn activated NADPH oxidase via the P2X7 receptor (P2X7R). Reactive oxygen species (ROS) production in fAbeta1-42- 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 fAbeta-stimulated microglia might be mediated by ATP released from the microglia. We therefore examined whether fAbeta1-42-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 microM) or oxidized ATP (100 microM) inhibited fAbeta-induced Ca2+ influx and reduced ROS generation to basal levels. Furthermore, ATP efflux from fAbeta1-42- 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.
authors.affiliation: Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Soo Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Moon
authors.forename: Hwan Goo
authors.initials: HG
authors.lastname: Lee
authors.forename: Seung Up
authors.initials: SU
authors.lastname: Kim
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017628:Microglia / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; C078639:amyloid beta-protein (1-38); C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate