Sava Irina G, Battaglia Valentina, Rossi Carlo A, Salvi Mauro, Toninello Antonio
Unità per lo Studio delle Biomembrane, Istituto di Neuroscienze del CNR, Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Free Radic Biol Med. 2006 Oct 15;41(8):1272-81. doi: 10.1016/j.freeradbiomed.2006.07.008. Epub 2006 Jul 15.
The isoflavonoid genistein, the cyclic triterpene glycyrrhetinic acid, and salicylate induce mitochondrial swelling and loss of membrane potential (Delta Psi) in rat liver mitochondria (RLM). These effects are Ca(2+)-dependent and are prevented by cyclosporin A and bongkrekik acid, classic inhibitors of mitochondrial permeability transition (MPT). This membrane permeabilization is also inhibited by N-ethylmaleimide, butylhydroxytoluene, and mannitol. The above-mentioned pro-oxidants also induce an increase in O(2) consumption and H(2)O(2) generation and the oxidation of sulfhydryl groups, glutathione, and pyridine nucleotides. All these observations are indicative of the induction of MPT mediated by oxidative stress. At concentrations similar to those present in the cell, spermine can prevent swelling and Delta Psi collapse, that is, MPT induction. Spermine, by acting as a free radical scavenger, in the absence of Ca(2+) inhibits H(2)O(2) production and maintains glutathione and sulfhydryl groups at normal reduced level, so that the critical thiols responsible for pore opening are also consequently prevented from being oxidized. Spermine also protects RLM under conditions of accentuated thiol and glutathione oxidation, lipid peroxidation, and protein oxidation, suggesting that its action takes place by scavenging the hydroxyl radical.
异黄酮染料木黄酮、环状三萜甘草次酸和水杨酸盐可诱导大鼠肝线粒体（RLM）发生线粒体肿胀并导致膜电位（ΔΨ）丧失。这些效应依赖于Ca(2+)，并可被环孢菌素A和膨润酸（线粒体通透性转换（MPT）的经典抑制剂）所阻止。这种膜通透性也受到N-乙基马来酰亚胺、丁基羟基甲苯和甘露醇的抑制。上述促氧化剂还可诱导O(2)消耗和H(2)O(2)生成增加以及巯基、谷胱甘肽和吡啶核苷酸的氧化。所有这些观察结果均表明氧化应激介导了MPT的诱导。在与细胞内浓度相似的情况下，精胺可防止肿胀和ΔΨ崩溃，即抑制MPT的诱导。在不存在Ca(2+)的情况下，精胺作为自由基清除剂，可抑制H(2)O(2)的产生，并使谷胱甘肽和巯基维持在正常的还原水平，从而也可防止负责孔开放的关键硫醇被氧化。在硫醇和谷胱甘肽氧化加剧、脂质过氧化和蛋白质氧化的条件下，精胺也可保护RLM，这表明其作用是通过清除羟基自由基来实现的。
