ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion
Experimental & Molecular Medicine
;
: 820-827, 2007.
Article
in English
| WPRIM
| ID: wpr-62081
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Peptide Fragments
/
Pyridoxal Phosphate
/
Cells, Cultured
/
Adenosine Triphosphate
/
Amyloid beta-Peptides
/
Reactive Oxygen Species
/
Rats, Sprague-Dawley
/
Receptors, Purinergic P2
/
Microglia
/
Autocrine Communication
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2007
Type:
Article
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