Effects of CDNF on 6-OHDA-induced apoptosis in PC12 cells via modulation of Bcl-2/Bax and caspase-3 activation
Effects of CDNF on 6-OHDA-induced apoptosis in PC12 cells via modulation of Bcl-2/Bax and caspase-3 activation
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DOI：
10.1007/s10072-014-1700-1
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发表时间：
2014-08-01
影响因子：
3.3
通讯作者：
Niu, Chao-shi
中科院分区：
文献类型：
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作者：
Mei, Jia-ming;Niu, Chao-shi
帕金森病（Parkinson's disease，PD）最显著的病理特征是黑质多巴胺神经元变性。目前，还没有治愈的方法，只有缓解PD症状的能力。保守的多巴胺神经营养因子（CDNF）在体内保护和拯救多巴胺神经元。然而，CDNF在PD中的分子功能仍不清楚。本研究探讨了CDNF对6-羟基多巴胺（6-OHDA）诱导的大鼠嗜铬细胞瘤（PC 12）细胞凋亡的预防和逆转作用及其内在机制。我们证明6-OHDA诱导PC 12细胞死亡，但CDNF以剂量依赖性方式减弱这种作用。进一步的研究表明，在CDNF预处理或处理后，Bcl-2/Bax比值上调，caspase-3活性下调，呈剂量依赖性，提示CDNF可能通过调节细胞凋亡的途径。这些数据表明，CDNF通过调节Bcl-2/Bax和caspase-3的活化来防止6-OHDA诱导的PC 12细胞凋亡。
Progressive dopamine neuron degeneration in the substantia nigra pars compacta is considered the most prominent pathological characteristic of Parkinson's disease (PD). Currently, there is no cure, but only the capability to relieve the symptoms of PD. The conserved dopamine neurotrophic factor (CDNF) protects and rescues dopamine neurons in vivo. However, the molecular function of CDNF in PD remains unclear. In present study, we investigated the role and intrinsic mechanism of CDNF in preventing and reversing rat pheochromocytoma (PC12) cells from apoptosis induced by 6-hydroxydopamine (6-OHDA). We demonstrate that 6-OHDA induces cell death in PC12 cells, but that CDNF attenuates this effect in a dose-dependent manner. Further study shows that upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity are observed in a dose-dependent manner upon pre-treatment or post-treatment with CDNF, suggesting a pathway of regulation of apoptosis by CDNF. These data demonstrate that CDNF prevents the apoptosis of PC12 cells induced by 6-OHDA by modulating Bcl-2/Bax and caspase-3 activation.