Evtodienko Y V, Teplova V V, Sidash S S, Ichas F, Mazat J P
Institute of Theoretical and Experimental Biophysics, Pushchino, Russian Federation.
FEBS Lett. 1996 Sep 9;393(1):86-8. doi: 10.1016/0014-5793(96)00875-7.
We report the effects of anticancer drugs, inhibitors of microtubule organisation, on the mitochondrial permeability transition pore (PTP) in Ehrlich ascites tumour cells. Taxol (5-20 microM) and colchicine (100-500 microM) prevented closing of the cyclosporin A-sensitive PTP. No taxol or colchicine effects on oxidative phosphorylation were observed in the range of concentrations used. We suggest that either membrane-bound tubulin per se can be part of PTP and/or the attachment of mitochondria to the microtubular network is essential for PTP regulation. The taxol inhibition of PTP closure, mediated through interaction with the cytoskeleton, sheds new light on the cytotoxic properties of this anticancer drug.
我们报告了抗癌药物（微管组织抑制剂）对艾氏腹水瘤细胞线粒体通透性转换孔（PTP）的影响。紫杉醇（5 - 20微摩尔）和秋水仙碱（100 - 500微摩尔）可阻止环孢菌素A敏感的PTP关闭。在所使用的浓度范围内，未观察到紫杉醇或秋水仙碱对氧化磷酸化有影响。我们认为，要么膜结合微管蛋白本身可成为PTP的一部分，和/或线粒体与微管网络的附着对于PTP调节至关重要。通过与细胞骨架相互作用介导的紫杉醇对PTP关闭的抑制作用，为这种抗癌药物的细胞毒性特性提供了新的线索。
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