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

✍ Scribed by Seok H. Hong; Hyun B. Choi; Seung U. Kim; James G. McLarnon

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 207 KB
• Volume: 83
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20829

✦ Synopsis

Abstract

We used calcium sensitive fluorescence microscopy to investigate the actions of PK11195, a ligand for the mitochondrial peripheral benzodiazepine receptor (PBR), to modulate Ca^2+^ influx through store‐operated channels (SOC) in human microglia. PK11195 effectively blocked SOC‐mediated Ca^2+^ influx induced by platelet‐activating factor (PAF) in a dose‐dependent manner (IC~50~ of 9 μM). A prolonged SOC‐mediated Ca^2+^ entry was also induced using the sarcoplasmic endoreticulum Ca^2+^‐ATPase (SERCA) inhibitor cyclopiazonic acid (CPA) to deplete intracellular endoplasmic reticulum (ER) stores; a single concentration of PK11195 (at 20 μM) reduced SOC‐mediated Ca^2+^ 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 Ca^2+^ through plasmalemmal SOC and subsequent modulation of cellular functions in human microglia. © 2006 Wiley‐Liss, Inc.