Expression of FasL and its interaction with Fas are mediated by c-Jun N-terminal kinase (JNK) pathway in 6-OHDA-induced rat model of Parkinson disease
Expression of FasL and its interaction with Fas are mediated by c-Jun N-terminal kinase (JNK) pathway in 6-OHDA-induced rat model of Parkinson disease
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DOI：
10.1016/j.neulet.2007.09.032
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发表时间：
2007-11-27
影响因子：
2.5
通讯作者：
Chen, Sheng-Di
中科院分区：
文献类型：
--
作者：
Pan, Jing;Zhao, Yan-Xin;Chen, Sheng-Di
我们和其他人的研究都强烈提示c-Jun n -末端激酶（JNK）信号通路在6-羟多巴胺（6-OHDA）诱导的黑质多巴胺能神经元损伤中起关键作用。然而，JNK在6-OHDA损伤中促凋亡作用的下游机制仍有待深入研究。Fas是一种具有促凋亡功能的肿瘤坏死因子受体家族成员，据报道，Fas在帕金森病（PD）患者的纹状体和黑质致密部（SNc）中升高。在本研究中，我们检测了大鼠PD模型中Fas配体（FasL）蛋白水平的变化及其与Fas的相互作用。我们发现，6-OHDA损伤后FasL的表达增加，而非Fas的表达增加；6-OHDA损伤增加了FasL与Fas的相互作用。这表明6- ohda诱导的Fas信号通路的激活是由JNK介导的，FasL可能是PD患者治疗方法中一个有希望的靶点。2007爱思唯尔爱尔兰有限公司版权所有。
Our previous studies and those of others have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in 6-hydroxydopamine (6-OHDA)-induced dopaminergic neuron injury in the substantia nigra. However, the downstream mechanism that accounts for the proapoptotic actions of JNK in 6-OHDA lesion remains to be investigated in detail. Fas, a member of the tumor necrosis factor receptor family with proapoptotic functions, was reported to be elevated within the striatum and substantia nigra pars compacta (SNc) of Parkinson's disease (PD) patients. In the present study, we examined the changes in the protein level of Fas ligand (FasL) and its interaction with Fas in a rat model of PD. We demonstrate that the expression of FasL and not Fas was increased after 6-OHDA lesion; additionally, the interaction of FasL and Fas was increased due to 6-OHDA lesion. This indicates that the 6-OHDA-induced activation of Fas signaling pathway is mediated by JNK and that FasL may be a promising target in the therapeutic approach for PD patients. (C) 2007 Elsevier Ireland Ltd. All rights reserved.