Interference with activity-dependent transcriptional activation of BDNF gene depending upon the expanded polyglutamines in neurons

Toshihide Miyashita, Akiko Tabuchi, Mamoru Fukuchi, Daichi Hara, Tomochika Kisukeda, Takayoshi Shimohata, Shoji Tsuji, Masaaki Tsuda*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

7 被引用数 (Scopus)

抄録

Expanded polyglutamines (polyQ) have been demonstrated to impair the CREB-dependent transcription in established cell lines. Since activity-dependent transcription in neurons, which plays an important role in forming neuronal plasticity, is largely controlled by CREB, it is important to study whether polyQ interferes with the activity-dependent transcriptional activation of genes in neurons. In cultured rat cortical neurons, over-expression of truncated dentatorubral-pallidoluysian atrophy proteins containing expanded polyQ, which form aggregation bodies in nucleus, reduced the calcium (Ca2+) signal-mediated transcriptional activation of brain-derived neurotrophic factor, c-fos, and pituitary adenylate cyclase-activating polypeptide gene promoters in a dose-dependent manner. The interference with the transcriptional activation was dependent upon the presence of polyQ, the strength of which was increased as the length of polyQ stretches was expanded. Thus, polyQ interferes with the activity-dependent transcription in a polyQ-length-dependent manner, which may correspond to the severity of polyglutamine diseases.

本文言語英語
ページ(範囲)1241-1248
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
333
4
DOI
出版ステータス出版済み - 2005/08/12

ASJC Scopus 主題領域

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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