Mitochondrial ligand inhibits store-operated calcium influx and COX-2 production in human microglia
Mitochondrial ligand inhibits store-operated calcium influx and COX-2 production in human microglia
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DOI：
10.1002/jnr.20829
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发表时间：
2006-05-15
影响因子：
4.2
通讯作者：
McLarnon, James G.
中科院分区：
文献类型：
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作者：
Hong, Seok H.;Choi, Hyun B.;McLarnon, James G.
我们使用钙敏感荧光显微镜来研究PK 11195（线粒体外周苯二氮卓受体（PBR）的配体）通过人类小胶质细胞中的钙池操纵通道（SOC）调节Ca 2+内流的作用。PK 11195以剂量依赖性方式有效地阻断血小板活化因子（PAF）诱导的SOC介导的Ca 2+内流（IC 50为9 μ M）。一个长期的SOC介导的Ca 2+进入也诱导使用肌质内质网Ca 2 +-ATP酶（SERCA）抑制剂cyclopiazonic酸（CPA）消耗细胞内内质网（ER）商店;一个单一浓度的PK 11195（在20 μ M）减少SOC介导的Ca 2+内流的78%。RT-PCR和免疫细胞化学分析结果显示，PK 11195还能抑制PAF刺激引起的环氧化酶2（考克斯-2）的表达和产生。这些结果表明，线粒体中PBR的激活与通过质膜SOC减少Ca 2+的进入和随后调节人小胶质细胞中的细胞功能有关。(c)2006 Wiley-Liss，Inc.
We used calcium sensitive fluorescence microscopy to investigate the actions of PK11195, a ligand for the mitochondrial periheral 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 2 manner (IC50 of 9 mu M). 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 mu M) 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 plasmalernmal SOC and subsequent modulation of cellular functions in human microglia. (c) 2006 Wiley-Liss, Inc.