Systemic administration of kainate (KA) stimulates glutamate receptors and renders animals to undergo robust seizures. This neuronal stimulation has both short-term and long-term effects on the gene expression of several transcription factors. Both CREB and AP-1 transcription factors play an important role in short-term modulation of most genes during seizures and neuronal damages. The AP-1 transcription complex composes of c-fos and fos-related antigens (FRA) and three jun proteins. It binds to the promoter regions of other genes and regulates their expression. We have found that the 35-37 kDa FRA proteins are the main forms of FRA proteins in the brain which expressed at least 5 months after one systemic injection of KA. Either Jun D or c-Jun is also detected in AP-1 DNA binding complex suggest that the FRA proteins expressed long-term changes for cellular adaptation in response to chronic or permanent changes. Genes related to neuronal plasticity may be targets for long-term FRA- containing AP-1 complexes. Regulation of proenkephalin transcription at ENKCRE 2 element via CREB/AP-1 transcription factors occurs by several second messenger systems. Flanking sites, AP-2 and ENKCRE 1 act indirectly to elevate pENK transcription. The 6-hydroxydopamine lesion at nigra region also increased the expression of 35-37 kDa protein at damaged side of striatum. Our first effort to clone 35-37 kDa transcript factor genes resulted in a M13 gene which codes a 63 kDa protein containing a leucine ZIP and a glutamine repeat in its deduced peptide sequence. However, the gene structure and function of the 35-37 kDa protein are not clear. Further work is necessary to clone and characterize this transcription factor.
