Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria.

Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria.
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DOI:
10.1016/j.freeradbiomed.2006.07.008
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发表时间:
2006-10
影响因子:
7.4
通讯作者:
I. Sava;V. Battaglia;C. Rossi;M. Salvi;A. Toninello
I. Sava;V. Battaglia;C. Rossi;M. Salvi;A. Toninello
中科院分区:
医学1区
文献类型:
--
作者:
I. Sava;V. Battaglia;C. Rossi;M. Salvi;A. Toninello

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在大鼠肝线粒体(RLM)中,染料木黄酮、环三萜类化合物大黄酸和水杨酸可诱导线粒体肿胀和膜电位(Δ E)损失。这些作用是Ca 2+依赖性的,并且被环孢菌素A和bongkrekik酸(线粒体通透性转换(MPT)的经典抑制剂)阻止。该膜透化也被N-乙基马来酰亚胺、丁基羟基甲苯和甘露醇抑制。上述促氧化剂还诱导O2消耗和H2 O2产生的增加以及巯基、谷胱甘肽和吡啶核苷酸的氧化。所有这些观察结果都表明氧化应激介导的MPT诱导。在与细胞中存在的浓度相似的浓度下,精胺可以防止肿胀和Δ Δ收缩,即MPT诱导。精胺,作为一种自由基清除剂,在没有钙离子的情况下,抑制H2 O2的产生,并保持谷胱甘肽和巯基在正常的还原水平,使关键的巯基负责孔开放,因此也防止被氧化。精胺也保护RLM的条件下加重硫醇和谷胱甘肽氧化,脂质过氧化和蛋白质氧化,表明其作用发生清除羟基自由基。
The isoflavonoid genistein, the cyclic triterpene glycyrrhetinic acid, and salicylate induce mitochondrial swelling and loss of membrane potential (ΔΨ) in rat liver mitochondria (RLM). These effects are Ca2+-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 O2consumption and H2O2generation 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 ΔΨ collapse, that is, MPT induction. Spermine, by acting as a free radical scavenger, in the absence of Ca2+inhibits H2O2production 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.