Transgenic mice expressing a dominant negative mutant interleukin-1beta converting enzyme show resistance to MPTP neurotoxicity.
Transgenic mice expressing a dominant negative mutant interleukin-1beta converting enzyme show resistance to MPTP neurotoxicity.
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DOI：
10.1097/00001756-199902250-00035
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发表时间：
1999-02
期刊：
影响因子：
1.7
通讯作者：
Peter Klevenyi;O. Andreassen;R. Ferrante;John R. Schleicher;R. Friedlander;M. Beal
中科院分区：
文献类型：
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作者：
Peter Klevenyi;O. Andreassen;R. Ferrante;John R. Schleicher;R. Friedlander;M. Beal
越来越多的证据表明细胞凋亡是神经退行性疾病中细胞死亡的主要机制。最近的证据表明，MPTP的长期给药可导致凋亡性细胞死亡。在本研究中，我们研究了表达白细胞介素-1 β转化酶（ICE）的显性负性抑制剂的转基因小鼠是否对MPTP诱导的神经毒性有抵抗力。MPTP导致同窝对照小鼠中多巴胺、DOPAC和HVA的显著消耗，而突变型白细胞介素-1 β转换酶小鼠中这些消耗被完全抑制。对MPTP诱导的酪氨酸羟化酶免疫反应神经元耗竭也有显着的保护作用。MPTP摄取或代谢无改变。这些结果提供了进一步的证据，凋亡细胞死亡以及ICE可能在MPTP的神经毒性中发挥重要作用。
Increasing evidence implicates apoptosis as a major mechanism of cell death in neurodegenerative diseases. Recent evidence has demonstrated that chronic administration of MPTP can lead to apoptotic cell death. In the present study we examined whether transgenic mice expressing a dominant negative inhibitor of interleukin-1beta convertase enzyme (ICE) are resistant to MPTP induced neurotoxicity. MPTP resulted in a significant depletion of dopamine, DOPAC and HVA in littermate control mice which were completely inhibited in the mutant interleukin-1beta converting enzyme mice. There was also significant protection against MPTP-induced depletion of tyrosine hydroxylase-immunoreactive neurons. There was no alteration in MPTP uptake or metabolism. These results provide further evidence that apoptotic cell death as well as ICE may play an important role in the neurotoxicity of MPTP.