Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor

被引：47

作者：

Cleary, Joanne

Johnson, Kathryn M.

Opipari, Anthony W.

Glick, Gary D.

机构：

[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Grad Program Immunol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 06期

关键词：

apoptosis; mitochondria; drug;

D O I：

10.1016/j.bmcl.2006.12.102

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

收藏

页码：1667 / 1670

页数：4

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