NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition: Implications for Huntington's disease
NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition: Implications for Huntington's disease
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DOI：
10.1016/j.neulet.2007.09.056
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发表时间：
2008-04-01
影响因子：
2.5
通讯作者：
Gulino, Alberto
中科院分区：
文献类型：
--
作者：
Napolitano, Maddalena;Zei, Daniela;Gulino, Alberto
核因子-kB（NF-kB）是DNA结合蛋白的一个家族，其是参与免疫和炎症反应以及细胞存活和凋亡的重要调节剂。在神经系统中，NF-kB在生理和病理条件下被激活，包括学习和记忆机制以及神经退行性疾病。NF-kB在神经元中响应于兴奋性毒性、代谢和氧化应激而被激活，并且有大量证据表明谷氨酸通过主要的离子型谷氨酸受体诱导NF-kB。在本研究中，3硝基丙酸（3 NP），琥珀酸脱氢酶（SD，复合物II）的不可逆抑制剂已被用来提供一个实验模型的亨廷顿病（HD）。具体来说，我们描述了3 NP诱导的激活NF-κ B和iNOS和nNOS基因在纹状体处理切片。为了更好地了解这些发现的失调基因和线粒体功能障碍之间的关系，我们在SK-N-MC人神经母细胞瘤细胞中研究了3 NP处理后，NF-κ B核转位和激活是否可能参与3 NP导致NOS基因转录激活的机制。这些结果是相关的，更精确地定义NF-κ B在神经元细胞中的作用，更好地理解其在神经退行性变中的假定参与。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Nuclear factor-kB (NF-kB) is a family of DNA-binding proteins that are important regulators involved in immune and inflammatory responses, as well as in cell survival and apoptosis. In the nervous system NF-kB is activated under physiological and pathological conditions including learning and memory mechanisms and neurodegenerative diseases. NF-kB is activated in neurons in response to excitotoxic, metabolic and oxidative stress and there is a body of evidence to suggest that glutamate induces NF-kB by the main ionotropic glutamate receptors. In the present study, 3 nitroproprionic acid (3NP), an irreversible inhibitor of succinate dehydrogenase (SD, complex II) has been employed to provide an experimental model of Huntington's disease (HD). Specifically, we described 3NP-induced activation of NF-kB and of iNOS and nNOS genes in striatal treated slices. To aim to better understand the relationship between these identified dysregulated genes and mitochondrial dysfunction, we investigated in SK-N-MC human neuroblastoma cells following 3NP treatment, whether NF-kB nuclear translocation and activation might be involved in the mechanisms by which 3NP leads to transcriptional activation of NOS genes. These results are relevant to more precisely define the role of NF-kB in neuronal cells and better understand its putative involvement in neurodegeneration. (C) 2007 Elsevier Ireland Ltd. All rights reserved.