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Protective action of tamoxifen on carboxyatractyloside-induced mitochondrial permeability transition.

机译:他莫昔芬对羧基白屈菜苷诱导的线粒体通透性转变的保护作用。

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AIMS: Mitochondrial permeability transition is established after massive Ca(2+) accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. MAIN METHODS: Permeability transition was assessed by analyzing matrix Ca(2+) release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. KEY FINDINGS: In freshly prepared mitochondria, tamoxifen, at the concentration of 10 muM, totally inhibited nonspecific membrane permeability induced by 1 muM carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. SIGNIFICANCE: Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug.
机译:目的:线粒体通透性转变是在基质中除诱导剂外大量Ca(2+)积累后建立的。可以通过二磷酸腺苷和免疫抑制剂环孢菌素A来完成孔的封闭。最近,雌激素拮抗剂他莫昔芬被引入作为通透性过渡孔开放的抑制剂。然而,该药物抑制孔开放的机理仍在讨论中。进行这项工作的目的是建立与他莫昔芬诱导的毛孔闭合有关的膜系统。为了这个目的,在加入与白蛋白核苷酸转位酶相互作用的特异试剂白术苷后诱导了通透性转变。主要方法:渗透性的过渡是通过分析基质Ca(2+)释放,跨膜电梯度和老年人以及新鲜制备的线粒体中的线粒体肿胀来评估的。而且,分析了膜线粒体和上清液中的细胞色素c含量。主要发现:在新鲜制备的线粒体中,他莫昔芬的浓度为10μM,完全抑制了1μM羧基白术苷诱导的非特异性膜通透性。此外,他莫昔芬抑制老年线粒体的非特异性通透性并减少膜的流动性。意义:可能认为,他莫昔芬对羧基白术苷诱导的非特异性膜通透性的抑制作用应归因于该药物的膜流动性降低。

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