The Accumulation of Arc(an Immediate Early Gene)mRNA by the Inhibition of Protein Synthesis

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Arc (activity-regulated cytoskeleton-associated protein) gene is one of the neuron-specific immediate early genes induced by neural activity. The regulation of Arc gene expression is unknown. We found that Arc mRNA is expressed constitutively in L929 cells, a mouse fibroblast cell line, and was, not transiently, increased by the calcium ionophore A23187. To address the induction of Arc mRNA by A23187, we isolated the mouse Arc gene and found that it consists of three exons, with the first exon including the whole coding region. We then constructed luciferase reporters fused with various 5 flanking regions of the mouse Arc gene. The reporter activities were not enhanced by A23187 in the tested regions up to about −9500 bp. As it is reported that protein synthesis is inhibited in by A23187, we treated L929 cells with a protein synthesis inhibitor, cycloheximide (CHX). The increase of Arc mRNA was induced by CHX alone in a calcium-independent manner and was comparable to that by A23187. No additive effect of A23187 was observed on the increase by CHX, whereas the additive effect was seen in PC12 cells. These results suggest that the inhibition of protein synthesis is a crucial factor for the accumulation of Arc mRNA in L929 cells.
社団法人日本薬理学会の論文
2003-03-01