Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus
Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus
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DOI：
10.1074/jbc.274.40.28106
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发表时间：
1999-10-01
影响因子：
4.8
通讯作者：
Kaczmarek, L
中科院分区：
文献类型：
--
作者：
Jaworski, J;Biedermann, IW;Kaczmarek, L
了解 AP-1 转录因子在中枢神经系统中的生物学功能可能会极大地受益于识别其靶基因。在这项研究中，我们提出了几条证据，表明 A9-1 可以调节啮齿动物海马组织金属蛋白酶-1 (timp-1) 基因的表达，以响应神经元兴奋的增加。这一观点得到了以下研究结果的支持：在红藻氨酸或戊四唑诱发的癫痫发作后，大鼠海马中发生timp-1 mRNA积累，与AP-1成分相比，时间进程延迟，并且与c-Fos蛋白（主要诱导AP-1成分）表达在空间上重叠。此外，在用任一促惊厥剂治疗大鼠后，源自timp-1启动子的AP-1序列与海马AP-1蛋白特异性结合。最后，timp-1启动子在体内（在携带timp-LacZ基因构建体的转基因小鼠中）和在体外在海马齿状回培养物的神经元中对兴奋性激活作出反应。这些发现表明AP-1转录因子可能通过影响细胞外基质重塑在大脑中发挥其作用。
Understanding of biological function of AP-1 transcription factor in central nervous system may greatly benefit from identifying its target genes. In this study, we present several lines of evidence implying A9-1 in regulating expression of tissue inhibitor of metalloproteinases-l (timp-1) gene in rodent hippocampus in response to increased neuronal excitation. Such a notion is supported by the findings that timp-1 mRNA accumulation occurs in the rat hippocampus after either kainate- or pentylenetetrazole-evoked seizures with a delayed, in comparison with AP-1 components, time course, as well as with spatial overlap with c-Fos protein (major inducible AP-1 component) expression. Furthermore, AP-1 sequence derived from timp-1 promoter is specifically bound by hippocampal AP-1 proteins after treating the rats with either pro-convulsive agent. Finally, timp-1 promoter responds to excitatory activation both in vivo, in transgenic mice harboring the timp-LacZ gene construct, and in vitro in neurons of the hippocampal dentate gyrus cultures, These findings suggest that the AP-1 transcription factor may exert its role in the brain through affecting extracellular matrix remodeling.