129 354

Cited 0 times in

Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar beta amyloid peptide (1-42)-stimulated microglia.

Authors
Moon, JH; Kim, SY; Lee, HG; Kim, SU; Lee, YB
Citation
Experimental & molecular medicine, 40(1):11-18, 2008
Journal Title
Experimental & molecular medicine
ISSN
1226-36132092-6413
Abstract
Recent studies have reported that the cholinergic anti-inflammatory pathway regulates peripheral inflammatory responses via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and that acetylcholine and nicotine regulate the expression of proinflammatory mediators such as TNF-alpha and prostaglandin E2 in microglial cultures. In a previous study we showed that ATP released by beta-amyloid-stimulated microglia induced reactive oxygen species (ROS) production, in a process involving the P2X(7) receptor (P2X(7)R), in an autocrine fashion. These observations led us to investigate whether stimulation by nicotine could regulate fibrillar beta amyloid peptide (1-42) (fAbeta1-42)-induced ROS production by modulating ATP efflux-mediated Ca(2+) influx through P2X(7)R. Nicotine inhibited ROS generation in fAbeta(1-42)-stimulated microglial cells, and this inhibition was blocked by mecamylamine, a non-selective nAChR antagonist, and a-bungarotoxin, a selective alpha7 nAChR antagonist. Nicotine inhibited NADPH oxidase activation and completely blocked Ca(2+) influx in fAbeta(1-42)-stimulated microglia. Moreover, ATP release from fAbeta(1-42)-stimulated microglia was significantly suppressed by nicotine treatment. In contrast, nicotine did not inhibit 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP)-induced Ca(2+) influx, but inhibited ROS generation in BzATP-stimulated microglia, indicating an inhibitory effect of nicotine on a signaling process downstream of P2X(7)R. Taken together, these results suggest that the inhibitory effect of nicotine on ROS production in fAbeta1-42-stimulated microglia is mediated by indirect blockage of ATP release and by directly altering the signaling process downstream from P2X(7)R.
MeSH terms
Adenosine Triphosphate/analogs & derivativesAdenosine Triphosphate/metabolismAdenosine Triphosphate/pharmacologyAmyloid/metabolism*Amyloid beta-Peptides/pharmacology*AnimalsCalcium/metabolismEnzyme Activation/drug effectsMicroglia/cytologyMicroglia/drug effects*Microglia/enzymologyMicroglia/metabolism*NADPH Oxidase/metabolismNicotine/pharmacologyNicotinic Antagonists/pharmacologyPeptide Fragments/pharmacology*RatsRats, Sprague-DawleyReactive Oxygen Species/metabolism*Receptors, Nicotinic/metabolism*Receptors, Purinergic P2/metabolismReceptors, Purinergic P2X7
DOI
10.3858/emm.2008.40.1.11
PMID
18305393
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
이, 용범
Full Text Link
Files in This Item:
emm-40-11-18.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse