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Mitochondrial ligand inhibits store-operated calcium influx and COX-2 production in human microglia.

Authors
Hong, SH; Choi, HB; Kim, SU; McLarnon, JG
Citation
Journal of neuroscience research, 83(7):1293-1298, 2006
Journal Title
Journal of neuroscience research
ISSN
0360-40121097-4547
Abstract
peripheral benzodiazepine receptor (PBR), to modulate Ca2+ influx through store-operated channels (SOC) in human microglia. PK11195 effectively blocked SOC-mediated Ca2+ influx induced by platelet-activating factor (PAF) in a dose-dependent manner (IC50 of 9 microM). A prolonged SOC-mediated Ca2+ entry was also induced using the sarcoplasmic endoreticulum Ca2+-ATPase (SERCA) inhibitor cyclopiazonic acid (CPA) to deplete intracellular endoplasmic reticulum (ER) stores; a single concentration of PK11195 (at 20 microM) reduced SOC-mediated Ca2+ influx by 78%. RT-PCR and immunocytochemical analysis results showed PK11195 also inhibited the expression and production of cyclooxygenase-2 (COX-2) triggered by PAF stimulation. These results suggest that activation of the PBR in mitochondria is linked to reduced entry of Ca2+ through plasmalemmal SOC and subsequent modulation of cellular functions in human microglia.
MeSH terms
Antineoplastic Agents/pharmacologyBrain/drug effectsBrain/metabolismCalcium Channels/drug effectsCalcium Channels/metabolism*Calcium Signaling/drug effectsCalcium Signaling/physiology*Calcium-Transporting ATPases/antagonists & inhibitorsCalcium-Transporting ATPases/metabolismCell Membrane/drug effectsCell Membrane/metabolismCells, CulturedCyclooxygenase 2/metabolism*Dose-Response Relationship, DrugEnzyme Inhibitors/pharmacologyHumansIndoles/pharmacologyIsoquinolines/pharmacologyLigandsMembrane Proteins/metabolism*Microglia/drug effectsMicroglia/metabolism*Microscopy, FluorescenceMitochondria/drug effectsMitochondria/metabolism*Platelet Activating Factor/metabolismPlatelet Activating Factor/pharmacologyRNA, Messenger/drug effectsRNA, Messenger/metabolismReceptors, GABA/drug effectsReceptors, GABA/metabolism*Sarcoplasmic Reticulum Calcium-Transporting ATPases
DOI
10.1002/jnr.20829
PMID
16547968
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
김, 승업
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