NAC-1 is a brain POZ/BTB protein that can prevent cocaine-induced sensitization in the rat
NAC-1 is a brain POZ/BTB protein that can prevent cocaine-induced sensitization in the rat
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DOI：
10.1523/jneurosci.20-16-06210.2000
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发表时间：
2000-08-15
影响因子：
5.3
通讯作者：
Kalivas, PW
中科院分区：
文献类型：
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作者：
Mackler, SA;Korutla, L;Kalivas, PW
在接触可卡因数周后，大鼠前脑中mRNA NAC - 1的水平升高。这种长期的神经适应性变化发生在行为敏化表达期间，行为敏化是精神兴奋剂诱导的偏执狂的一种模型。NAC - 1是由这种受可卡因调节的mRNA编码的蛋白质，包含一个痘病毒和锌指/矮脚鸡与有轨电车轨道及广泛复合物（POZ/BTB）基序，该基序介导几种转录调节因子之间的相互作用。目前的研究表明，NAC - 1作为一种转录因子发挥作用。NAC - 1定位于大脑神经元的细胞核。在细胞培养中，转染NAC - 1可抑制报告基因的转录。在哺乳动物双杂交研究中，NAC - 1还能够影响其他POZ/BTB蛋白的作用；这些相互作用需要POZ/BTB结构域的存在。然而，NAC - 1似乎是一种独特的POZ/BTB转录调节因子，因为它不包含在其他这些DNA结合蛋白中发现的任何锌指区域。通过腺病毒介导在大鼠伏隔核中过表达NAC - 1蛋白，可阻止因重复给予可卡因而产生的行为敏化的发展，但不影响其表达。因此，NAC - 1可能通过调节哺乳动物大脑中的基因转录来改变精神兴奋剂滥用的长期行为。
Levels of the mRNA NAC-1 are increased in the rat forebrain weeks after cocaine exposure. This long-term neuroadaptation occurs during the expression of behavioral sensitization, a model of psychostimulant-induced paranoia. NAC-1, the protein encoded by this cocaine-regulated mRNA, contains a Pox virus and zinc finger/bric-a-brac tramtrack broad complex (POZ/BTB) motif, which mediates interactions among several transcriptional regulators. The present studies demonstrate that NAC-1 acts as a transcription factor. NAC-1 was localized to the nucleus of neurons in the brain. Transfection of NAC-1 in cell culture repressed transcription of a reporter gene. NAC-1 was also able to affect the actions of other POZ/BTB proteins in mammalian two-hybrid studies; these interactions required the presence of the POZ/BTB domain. However, NAC-1 appears to be a unique POZ/BTB transcriptional regulator because it does not contain any zinc finger regions found in these other DNA-binding proteins. Adenoviral-mediated overexpression of NAC-1 protein in the rat nucleus accumbens prevented the development but not the expression of behavioral sensitization produced by repeated administration of cocaine. Thus, NAC-1 may modify the longterm behaviors of psychostimulant abuse by regulating gene transcription in the mammalian brain.