Neuroprotective Effect of Quercetin Against Hydrogen Peroxide-induced Oxidative Injury in P19 Neurons
Neuroprotective Effect of Quercetin Against Hydrogen Peroxide-induced Oxidative Injury in P19 Neurons
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DOI：
10.1007/s12031-012-9737-1
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发表时间：
2012-06-01
影响因子：
3.1
通讯作者：
Orsolic, Nada
中科院分区：
文献类型：
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作者：
Jembrek, Maja Jazvinscak;Vukovic, Lidija;Orsolic, Nada
氧化应激与多种神经退行性疾病中的神经元死亡有关。在本研究中，P19神经元获得的分化程序从小鼠畸胎瘤P19细胞被用来调查的能力，槲皮素，植物衍生的黄酮类化合物，防止神经元死亡诱导暴露于150 μ M或1.5 mM过氧化氢（H2 O2）24小时。槲皮素治疗改善了暴露于两种类型的氧化损伤的P19神经元的活力。在适度的氧化应激过程中，槲皮素减少了活性氧（ROS）的产生，并防止H2 O2诱导的核凝聚，caspase 3/7活性的增加和聚（APD-核糖）聚合酶表达的上升。Bcl-2家族成员Bax和Bcl-2的表达在转录和翻译水平均不受槲皮素处理的影响。在严重的氧化损伤，槲皮素阻止过氧化氢诱导的ROS积累和细胞膜完整性和核形态的变化上升。所获得的结果表明，槲皮素的神经保护作用与其抗氧化作用和预防与程序性细胞死亡级联相关的事件有关。鉴于这些发现，人们可能会认为槲皮素对预防人类衰老和年龄相关性神经退行性疾病中氧化应激驱动的神经元损失具有有益作用。
Oxidative stress is implicated in neuronal death in a variety of neurodegenerative diseases. In the present study, P19 neurons obtained by the differentiation procedure from mouse teratocarcinoma P19 cells were used to investigate the ability of quercetin, a plant-derived flavonoid, to prevent neuronal death induced by exposure to 150 mu M or 1.5 mM hydrogen peroxide (H2O2) for 24 h. Quercetin treatment improved viability of P19 neurons exposed to both types of oxidative injury. During the modest oxidative stress, quercetin diminished generation of reactive oxygen species (ROS) and prevented H2O2-induced nuclear condensation, increase in caspase 3/7 activity and rise in poly(APD-ribose) polymerase expression. Expression of Bcl-2 family members Bax and Bcl-2 was not affected by quercetin treatment at both the transcriptional and translational levels. During the severe oxidative injury, quercetin prevented H2O2-induced rise in ROS accumulation and changes in plasma membrane integrity and nuclear morphology. The obtained results suggest that neuroprotective effects of quercetin are related to its antioxidative action and prevention of events associated with programmed cell death cascade. In the light of these findings, one might assume beneficial effects of quercetin for the prevention of oxidative stress-driven neuronal loss in human aging and age-related neurodegenerative diseases.