24-Epibrassinolide, a Phytosterol from the Brassinosteroid Family, Protects Dopaminergic Cells against MPP-Induced Oxidative Stress and Apoptosis.

24-Epibrassinolide, a Phytosterol from the Brassinosteroid Family, Protects Dopaminergic Cells against MPP-Induced Oxidative Stress and Apoptosis.
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DOI:
10.1155/2011/392859
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发表时间:
2011
影响因子:
2.9
通讯作者:
Martinoli MG
Martinoli MG
中科院分区:
其他
文献类型:
--
作者:
Carange J;Longpré F;Daoust B;Martinoli MG

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氧化应激和细胞凋亡经常被用来解释各种神经退行性疾病的神经细胞损伤,如帕金森S病。油菜素类固醇(BRs)是公认的植物甾醇,通过调节抗氧化酶的级联反应来提高蔬菜的抗逆性。然而,到目前为止,它们对哺乳动物神经细胞的抗氧化作用还没有被研究过。我们分析了24-表油菜素内酯(24-Epi)对1-甲基-4-苯基吡啶(MPP+-)诱导的多巴胺能神经元氧化应激和随后的细胞凋亡的保护作用。我们的结果表明,24-Epi降低了细胞内的活性氧水平,调节了超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。最后,我们确定24-Epi的抗氧化特性通过减少DNA片段化、Bax/Bcl2蛋白比率和切割的caspase-3来抑制MPP+诱导的细胞凋亡。这是首次在哺乳动物神经细胞系中显示24-Epi的强大抗氧化剂和神经保护作用。
Oxidative stress and apoptosis are frequently cited to explain neuronal cell damage in various neurodegenerative disorders, such as Parkinson' s disease. Brassinosteroids (BRs) are phytosterols recognized to promote stress tolerance of vegetables via modulation of the antioxidative enzyme cascade. However, their antioxidative effects on mammalian neuronal cells have never been examined so far. We analyzed the ability of 24-epibrassinolide (24-Epi), a natural BR, to protect neuronal PC12 cells from 1-methyl-4-phenylpyridinium- (MPP+-) induced oxidative stress and consequent apoptosis in dopaminergic neurons. Our results demonstrate that 24-Epi reduces the levels of intracellular reactive oxygen species and modulates superoxide dismutase, catalase, and glutathione peroxidase activities. Finally, we determined that the antioxidative properties of 24-Epi lead to the inhibition of MPP+-induced apoptosis by reducing DNA fragmentation as well as the Bax/Bcl-2 protein ratio and cleaved caspase-3. This is the first time that the potent antioxidant and neuroprotective role of 24-Epi has been shown in a mammalian neuronal cell line.
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