Adams David S, Hasson Brendan, Boyer-Boiteau Anne, El-Khishin Adam, Shashoua Victor E
Department of Biology/Biotechnology, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, USA.
J Neurosci Res. 2003 May 1;72(3):405-16. doi: 10.1002/jnr.10590.
Ependymin (EPN) is a goldfish brain neurotrophic factor previously shown to function in a variety of cellular events related to long-term memory formation and neuronal regeneration. CMX-8933, an 8-amino-acid synthetic peptide fragment of EPN, was designed for aiding an investigation of the biological properties of this glycoprotein. We reported from previous studies that treatment of mouse neuroblastoma (NB2a) cultures with CMX-8933 promotes activation of transcription factor AP-1, a characteristic previously associated with the following full-length neurotrophic factors: nerve growth factor, neurotropin-3, and brain-derived neurotrophic factor. The CMX-8933-activated AP-1 specifically bound an AP-1 consensus probe and appeared to contain c-Jun and c-Fos protein components in antibody supershift experiments. Because AP-1 influences a variety of positive and negative cellular processes, determined in part by its exact protein composition and mechanism of activation, we extended these initial AP-1 observations in the current study to confirm the identity of the CMX-8933-activated c-Jun and c-Fos components. CMX-8933 increases the enzymatic activity of c-Jun N-terminal kinase (JNK), increases the phosphorylation of JNK and c-Jun proteins, and increases the cellular titers of c-Jun and c-Fos mRNAs. Furthermore, the AP-1 activated by CMX-8933 is functional, insofar as it transactivates both synthetic and natural AP-1-dependent reporter plasmids. Inhibition studies indicate that activation of the 8933-induced AP-1 occurs via the mitogen-activated protein kinase pathway. These data are in agreement with the recently proposed model for the conversion of short- to long-term synaptic plasticity and memory, in which a JNK-activated transcription factor AP-1, containing c-Jun and c-Fos components, functions at the top of a hierarchy of transcription factors known to regulate long-term neural plasticity.
室管膜素（EPN）是一种金鱼脑神经营养因子，先前已证明其在与长期记忆形成和神经元再生相关的多种细胞事件中发挥作用。CMX - 8933是EPN的一个8氨基酸合成肽片段，旨在辅助研究这种糖蛋白的生物学特性。我们先前的研究报道，用CMX - 8933处理小鼠神经母细胞瘤（NB2a）培养物可促进转录因子AP - 1的激活，这一特征先前与以下全长神经营养因子相关：神经生长因子、神经营养素 - 3和脑源性神经营养因子。在抗体超迁移实验中，CMX - 8933激活的AP - 1特异性结合AP - 1共有探针，且似乎包含c - Jun和c - Fos蛋白成分。由于AP - 1影响多种正向和负向细胞过程，部分由其确切的蛋白质组成和激活机制决定，我们在当前研究中扩展了这些最初关于AP - 1的观察结果，以确认CMX - 8933激活的c - Jun和c - Fos成分的身份。CMX - 8933增加c - Jun氨基末端激酶（JNK）的酶活性，增加JNK和c - Jun蛋白的磷酸化，并增加c - Jun和c - Fos mRNA的细胞水平。此外，CMX - 8933激活的AP - 1具有功能，因为它能反式激活合成的和天然的AP - 1依赖性报告质粒。抑制研究表明，8933诱导的AP - 1的激活是通过丝裂原活化蛋白激酶途径发生的。这些数据与最近提出的短期到长期突触可塑性和记忆转换模型一致，在该模型中，由c - Jun和c - Fos成分组成的JNK激活转录因子AP - 1在已知调节长期神经可塑性的转录因子层级中处于顶端发挥作用。
