초록 열기/닫기 버튼
Present study demonstrated that fibrillar β-amyloid peptide (fAβ1-42) induced ATP release, which in turn ac-tivated 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 ex-tracellular Ca2+. Considering previous observation of superoxide generation by Ca2+ influx through P2X7R in fAβ-stimulated microglia might be mediated by ATP re-leased 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 an-tagonists Pyridoxal-phosphate-6-azophenyl-2',4'- di-sulfonate (100 M) or oxidized ATP (100 M) inhibited fAβ-induced Ca2+ influx and reduced ROS generation to basal levels. Furthermore, ATP efflux from fAβ1-42- stimulated microglia was observed, and apyrase treat-ment decreased the generation of ROS. These findings provide conclusive evidence that fAβ-stimulated ROS generation in microglial cells is regulated by ATP re-leased from the microglia in an autocrine manner.
키워드열기/닫기 버튼
adenosine triphosphate; Alzheimer's dis-ease; amyloid β-protein; calcium; microglia; NADPH oxidase; purinoceptor P2Z; reactive oxygen species
