Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor
Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor
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DOI：
10.1016/j.bmcl.2006.12.102
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发表时间：
2007-03-15
影响因子：
2.7
通讯作者：
Glick, Gary D.
中科院分区：
文献类型：
--
作者：
Cleary, Joanne;Johnson, Kathryn M.;Glick, Gary D.
尽管PK 11195以纳摩尔亲和力与外周苯二氮卓类受体结合，但存在显著数据表明其具有不同于PBR的另一种细胞靶点。在这里，我们证明，PK 11195抑制F1 F0-ATP酶活性的OSCP依赖性的方式，类似于促凋亡苯二氮卓类Bz-423。重要的是，我们的数据表明，用微摩尔浓度的PK 11195观察到的细胞反应（通常归因于PBR的调节）可能是线粒体F1 F0-ATP酶抑制的直接结果。(c)2007爱思唯尔有限公司版权所有。
Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F1F0-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodiazepine Bz-423. Importantly, our data indicate that cellular responses observed with micromolar concentrations of PK11195, which are commonly attributed to modulation of the PBR, are likely a direct result of mitochondrial F1F0-ATPase inhibition. (c) 2007 Elsevier Ltd. All rights reserved.