Involvement of ubiquitin proteasome system in protective mechanisms of Puerarin to MPP+-elicited apoptosis
Involvement of ubiquitin proteasome system in protective mechanisms of Puerarin to MPP+-elicited apoptosis
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DOI：
10.1016/j.neures.2008.10.009
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发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Li, Qing-Lin
中科院分区：
文献类型：
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作者：
Cheng, Yue-Fa;Zhu, Guo-Qi;Li, Qing-Lin
有充分证据表明，神经元中泛素蛋白酶体系统（UPS）的功能障碍会加剧帕金森病（PD）。然而，UPS是否参与葛根素对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPP+)引起的细胞死亡的保护作用尚待阐明。在本研究中，用 1 mM MPP+ 处理 SH-SY5Y 细胞会引发特征性细胞凋亡，而葛根素预处理可保护细胞免受 MPP+ 诱导的细胞凋亡，这通过促进细胞活力、改善形态变化和降低细胞凋亡率来证明。为了进一步探讨葛根素在MPP+诱导的SH-SY5Y细胞死亡中的潜在保护机制，检测了UPS活性、线粒体依赖性细胞凋亡和caspase-3活性。葛根素预处理可减弱 MPP+ 诱导的蛋白酶活性功能障碍，从而减少泛素结合蛋白的积累。同时，葛根素显着减弱caspase-3活性。此外，与MPP+治疗组相比，葛根素增加了bcl-2/bax的比率。综上所述，这些结果表明葛根素可以通过调节 UPS 的功能来保护 MPP+ 诱导的 SH-SY5Y 细胞免于凋亡。 (C) 2008 Elsevier Ireland Ltd 和日本神经科学学会。版权所有。
It has been well documented that dysfunction of ubiquitin proteasome system (UPS) in the neuron exacerbated the Parkinson's disease (PD). However, whether or not UPS is involved in the protective effect of Puerarin on 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPP+)-elicited cell death is yet to be elucidated. In this study, treatment of SH-SY5Y cells with 1 mM MPP+-elicited a characteristic apoptotic cell death and pretreatment with Puerarin protected cells against MPP+-induced apoptosis as evidenced by promoting cell viability, improving morphological changes and reducing apoptotic rate. To further explore the potential protective mechanism of Puerarin in MPP+-induced SH-SY5Y cell death, UPS activity, mitochondria-dependent apoptosis and caspase-3 activity were measured. Puerarin pretreatment attenuated MPP+-induced dysfunction of protease activity, thereby reducing accumulation of ubiquitin-conjugated proteins. Meanwhile, caspase-3 activity was remarkably attenuated by Puerarin. In addition, the ratio of bcl-2/bax was increased by Puerarin in comparison with MPP+-treated group. Taken together, these results suggest that Puerarin Could protect MPP+-induced SH-SY5Y cells from apoptosis by regulating the function of UPS. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.