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首页> 外文期刊>Biochemistry >Mitochondrial Models of Pathologies with Oxidative Stress. Efficiency of Alkalization to Reduce Mitochondrial Damage
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Mitochondrial Models of Pathologies with Oxidative Stress. Efficiency of Alkalization to Reduce Mitochondrial Damage

机译:氧化应激病理的线粒体模型。碱化减少线粒体损伤的效率

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摘要

Previously, we developed a method to monitor the development of oxidative stress in isolated liver mitochondria. The method is based on recording of membrane potential changes in response to sequential introduction of low concentrations (5-20 μM) of tert-butyl hydroperoxide (tBHP). It allows monitoring of the extent of amplification or attenuation of oxidative stress caused by external influences (changes in incubation conditions, additions of biologically active substances). Based on this method, we created a mitochondrial model for the study and improvement of treatment of pathologies associated with oxidative stress. The following two processes were simulated in the experiments: 1) introduction of desferal for treatment of serious diseases caused by cell overload with iron (high desferal concentrations were shown to suppress mitochondrial energetics); 2) efficiency of alkalization to reduce mitochondrial damage induced by oxidative stress. The experiments have shown that even a small increase in pH (alkalization) increases the amount of tBHP that can be added to mitochondria before the MPTP ("mitochondrial permeability transition pore") is induced. The effect of alkalization was shown to be close to the effect of cyclosporin A in the pH range 7.2-7.8. The mechanism of the similarities of these effects in the ? organism and in mitochondrial suspensions is explained by the increase in toxic reactive oxygen species in both systems under oxidative stress.
机译:以前,我们开发了一种方法来监测孤立的肝线粒体中氧化应激的发展。该方法基于记录对低浓度(5-20​​μM)的叔丁基氢过氧化物(tBHP)的顺序引入产生响应的膜电势变化。它允许监视由外部影响(孵育条件的变化,生物活性物质的添加)引起的氧化应激的放大或减弱的程度。基于此方法,我们创建了线粒体模型,用于研究和改善与氧化应激相关的病理学治疗。在实验中模拟了以下两个过程:1)引入去铁皮治疗铁引起的细胞超负荷引起的严重疾病(显示高的去铁皮浓度可抑制线粒体能量)。 2)碱化的效率,以减少氧化应激引起的线粒体损伤。实验表明,即使在pH值小幅增加(碱化)的情况下,在诱导MPTP(“线粒体通透性转换孔”)之前,可以添加到线粒体中的tBHP的量也会增加。在碱度为7.2-7.8时,碱化作用与环孢菌素A接近。这些效应的相似性机制在?在氧化应激下,两个系统中有毒的活性氧物种的增加都可以解释这种生物体和线粒体悬浮液中的生物。

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