Rylski Marcin, Amborska Renata, Zybura Katarzyna, Michaluk Piotr, Bielinska Beata, Konopacki Filip A, Wilczynski Grzegorz M, Kaczmarek Leszek
Department of Molecular and Cellular Neurobiology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland.
Mol Cell Neurosci. 2009 Jan;40(1):98-110. doi: 10.1016/j.mcn.2008.09.005. Epub 2008 Oct 11.
Matrix Metalloproteinase-9 (MMP-9) is an extracellularly operating enzyme involved in the synaptic plasticity, hippocampal-dependent long term memory and neurodegeneration. Previous studies have shown its upregulation following seizure-evoking stimuli. Herein, we show that in the rat brain, MMP-9 mRNA expression in response to pentylenetetrazole-evoked neuronal depolarization is transient. Furthermore, we demonstrate that in the rat hippocampus neuronal activation strongly induces JunB expression, simultaneously leading to an accumulation of JunB/FosB complexes onto the -88/-80 bp site of the rat MMP-9 gene promoter in vivo. Surprisingly, manipulations with JunB expression levels in activated neurons revealed its moderate repressive action onto MMP-9 gene expression. Therefore, our study documents the active repressive influence of AP-1 onto MMP-9 transcriptional regulation by the engagement of JunB.
基质金属蛋白酶-9（MMP-9）是一种参与突触可塑性、海马依赖性长期记忆和神经退行性变的细胞外作用酶。先前的研究表明，在诱发癫痫的刺激后其表达上调。在此，我们表明，在大鼠脑中，对戊四氮诱发的神经元去极化反应时，MMP-9 mRNA表达是短暂的。此外，我们证明，在大鼠海马中，神经元激活强烈诱导JunB表达，同时导致JunB/FosB复合物在体内大鼠MMP-9基因启动子的-88/-80 bp位点上积累。令人惊讶的是，对激活神经元中JunB表达水平的操作揭示了其对MMP-9基因表达的适度抑制作用。因此，我们的研究记录了AP-1通过JunB的参与对MMP-9转录调控的积极抑制影响。
