Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity
Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity
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7,8-二羟基黄酮的抗氧化作用可保护 PC12 细胞免受 6-羟基多巴胺诱导的细胞毒性
DOI：
10.1016/j.neuint.2013.10.018
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Qu, Zhiqiang
中科院分区：
文献类型：
--
作者：
Han, Xiaohua;Zhu, Shaolei;Qu, Zhiqiang
氧化应激诱导的神经元死亡在神经退行性疾病的发病机制中起着关键作用。近年来，7，8-二羟基黄酮（7，8-DHF）作为一种选择性酪氨酸激酶受体B（Trk B）激动剂，具有神经保护作用。此外，7，8-DHF的抗氧化作用可保护神经细胞免受氧化损伤。在本研究中，我们使用PC 12细胞，一种通常被认为缺乏TrkB的细胞系，来研究7，8-DHF对6-羟基多巴胺（6-OHDA）诱导的细胞毒性的影响及其潜在机制。我们发现，7，8-DHF有效地防止了6-OHDA诱导的细胞死亡、凋亡和线粒体功能障碍。在无细胞系统中，7，8-DHF不减缓细胞外6-OHDA的自氧化，其可产生H2 O2。然而，我们发现7，8-DHF显著降低细胞丙二醛含量和磷酸化组蛋白H2A.X蛋白水平。7，8-DHF也提高6-OHDA处理的细胞中的总超氧化物歧化酶活性。这些结果表明，7，8-DHF可能通过其强大的抗氧化活性保护PC 12细胞免受6-OHDA诱导的细胞毒性。通过作为一种有效的TrkB激动剂和抗氧化剂以及其易于穿过血脑屏障，7，8-DHF可能被开发为治疗神经退行性疾病的有希望的候选物。(C)2013爱思唯尔有限公司保留所有权利。
Oxidative stress-induced neuronal death plays a pivotal role in pathogenesis of neurodegenerative disorders. Recently, 7,8-dihydroxyflavone (7,8-DHF) has been shown to exert neuroprotective effects by acting as a selective tyrosine kinase receptor B (TrkB) agonist In addition, the antioxidant action of 7,8-DHF may protect neuronal cells against oxidative injury. In the present study, we used PC12 cells, a cell line generally thought to lack TrkB, to investigate the effect of 7,8-DHF on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and the underlying mechanism. We found that 7,8-DHF effectively prevented cell death, apoptosis and mitochondrial dysfunction induced by 6-OHDA. In a cell free system, 7,8-DHF did not slow down extracellular auto-oxidation of 6-OHDA which may generate H2O2. However, We found that 7,8-DHF dramatically reduced cellular malondialdehyde content and phospho-histone H2A.X protein level. 7,8-DHF also elevated total superoxide dismutase activity in 6-OHDA-treated cells. These results indicate that 7,8-DHF might protect PC12 cells against 6-OHDA-induced cytotoxicity through its powerful antioxidant activity. By acting as a potent TrkB agonist and an antioxidant together with its easiness to pass across blood-brain barrier, 7,8-DHF may be developed into a promising candidate in treatment of neurodegenerative diseases. (C) 2013 Elsevier Ltd. All rights reserved.