ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion.
- Author:
Soo Yoon KIM
1
;
Ju Hyun MOON
;
Hwan Goo LEE
;
Seung Up KIM
;
Yong Beom LEE
Author Information
1. Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-721, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
adenosine triphosphate;
Alzheimer's disease;
amyloid beta-protein;
calcium;
microglia;
NADPH oxidase;
purinoceptor P2Z;
reactive oxygen species
- MeSH:
Adenosine Triphosphate/*metabolism;
Amyloid beta-Protein/*pharmacology;
Animals;
Autocrine Communication/*drug effects/physiology;
Cells, Cultured;
Microglia/*drug effects;
Peptide Fragments/*pharmacology;
Pyridoxal Phosphate/analogs & derivatives/metabolism;
Rats;
Rats, Sprague-Dawley;
Reactive Oxygen Species/*metabolism;
Receptors, Purinergic P2/physiology
- From:Experimental & Molecular Medicine
2007;39(6):820-827
- CountryRepublic of Korea
- Language:English
-
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.
