寡霉素是H⁺-ATP合酶F0部分的抑制剂，可抑制肿瘤坏死因子诱导的细胞凋亡。

Oligomycin, inhibitor of the F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis.

作者信息

Shchepina Liarisa A, Pletjushkina Olga Y, Avetisyan Armine V, Bakeeva Liora E, Fetisova Elena K, Izyumov Denis S, Saprunova Valeria B, Vyssokikh Mikhail Y, Chernyak Boris V, Skulachev Vladimir P

机构信息

AN Belozersky Institute, MV Lomonosov Moscow State University, 4 Khokhlova str., Bldg, A, Moscow 119992, Russia.

出版信息

Oncogene. 2002 Nov 21;21(53):8149-57. doi: 10.1038/sj.onc.1206053.

DOI:10.1038/sj.onc.1206053

PMID:12444550

Abstract

The release of cytochrome c from the intermembrane space of mitochondria into the cytosol is one of the critical events in apoptotic cell death. In the present study, it is shown that release of cytochrome c and apoptosis induced by tumor necrosis factor alpha (TNF) in HeLa cells can be inhibited by (i) overexpression of an oncoprotein Bcl-2, (ii) Cyclosporin A, an inhibitor of the mitochondrial permeability transition pore (PTP) or (iii) oligomycin, an inhibitor of H+- ATP-synthase. Staurosporine-induced apoptosis is sensitive to Bcl-2 but insensitive to Cyclosporin A and oligomycin. The effect of oligomycin is not due to changes in mitochondrial membrane potential or to inhibition of ATP synthesis/hydrolysis since (a) uncouplers (CCCP, DNP) which discharge the membrane potential fail to abolish the protective action of oligomycin and (b) aurovertin B (another inhibitor of H+-ATP-synthase, affecting its F1 component) do not affect apoptosis. A role of oligomycin-sensitive F0 component of H+-ATP-synthase in the TNF-induced PTP opening and apoptosis is suggested.

摘要

细胞色素c从线粒体膜间隙释放到细胞质中是凋亡性细胞死亡的关键事件之一。在本研究中，结果表明，在HeLa细胞中，细胞色素c的释放以及由肿瘤坏死因子α（TNF）诱导的凋亡可被以下因素抑制：（i）癌蛋白Bcl-2的过表达；（ii）环孢菌素A，一种线粒体通透性转换孔（PTP）抑制剂；或（iii）寡霉素，一种H⁺-ATP合酶抑制剂。星形孢菌素诱导的凋亡对Bcl-2敏感，但对环孢菌素A和寡霉素不敏感。寡霉素的作用并非由于线粒体膜电位的改变或ATP合成/水解的抑制，因为（a）使膜电位去极化的解偶联剂（CCCP、DNP）未能消除寡霉素的保护作用，且（b）金担子素B（另一种H⁺-ATP合酶抑制剂，影响其F1组分）不影响凋亡。提示H⁺-ATP合酶的寡霉素敏感F0组分在TNF诱导的PTP开放和凋亡中起作用。