Salvi Mauro, Brunati Anna Maria, Clari Giulio, Toninello Antonio
Dipartimento di Chimica Biologica, Istituto di Neuroscienze del C.N.R., Unità per lo Studio delle Biomembrane, Università di Padova, Via G. Colombo 3, 35121, Padova, Italy.
Biochim Biophys Acta. 2002 Dec 2;1556(2-3):187-96. doi: 10.1016/s0005-2728(02)00361-4.
Genistein, a natural isoflavone present in soybeans, is a potent agent in the prophylaxis and treatment of cancer. Addition of genistein to isolated rat liver mitochondria (RLM) induces swelling, loss of membrane potential and release of accumulated Ca2+. These changes are Ca2+-dependent and are prevented by cyclosporin A (CsA) and bongkrekic acid (BKA), two classical inhibitors of the mitochondrial permeability transition (MPT). Induction of the MPT by genistein is accompanied by oxidation of thiol groups and pyridine nucleotides. The reducing agent dithioerythritol and the alkylating agent N-ethylmaleimide (NEM) completely prevent the opening of the transition pore, thereby emphasizing that the effect of the isoflavone correlates with the mitochondrial redox state. Further analyses showed that genistein induces the MPT by the generation of reactive oxygen species (ROS) due to its interaction with the respiratory chain at the level of mitochondrial complex III.
染料木黄酮是大豆中存在的一种天然异黄酮，是预防和治疗癌症的一种有效物质。向分离的大鼠肝线粒体（RLM）中添加染料木黄酮会导致肿胀、膜电位丧失以及积累的Ca2+释放。这些变化是Ca2+依赖性的，并可被环孢菌素A（CsA）和邦克酸（BKA）这两种线粒体通透性转换（MPT）的经典抑制剂所阻止。染料木黄酮诱导MPT的过程伴随着巯基和吡啶核苷酸的氧化。还原剂二硫苏糖醇和烷基化剂N-乙基马来酰亚胺（NEM）完全阻止了转换孔的开放，从而强调了异黄酮的作用与线粒体氧化还原状态相关。进一步分析表明，染料木黄酮由于其在线粒体复合物III水平与呼吸链相互作用而产生活性氧（ROS），从而诱导MPT。
