Regulatory role of neuron-restrictive silencing factor in expression of TRPC1

Takayoshi Ohba, Hiroyuki Watanabe, Yoichiro Takahashi, Takashi Suzuki, Ichiro Miyoshi, Shinnsuke Nakayama, Eisaku Satoh, Kenji Iino, Hironobu Sasano, Yasuo Mori, Sadao Kuromitsu, Keiichi Imagawa, Yoshihiko Saito, Toshihiko Iijima, Hiroshi Ito, Manabu Murakami

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca2+ channel (SOCC)-mediated Ca2+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT activation. Our findings strongly suggest that NRSF regulates TRP1 gene expression and causes changes in the levels of calcium entry through SOCCs.

Original languageEnglish
Pages (from-to)764-770
Number of pages7
JournalBiochemical and biophysical research communications
Volume351
Issue number3
DOIs
Publication statusPublished - 2006 Dec 22

Keywords

  • NRSF
  • SOC
  • TRPC1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ohba, T., Watanabe, H., Takahashi, Y., Suzuki, T., Miyoshi, I., Nakayama, S., Satoh, E., Iino, K., Sasano, H., Mori, Y., Kuromitsu, S., Imagawa, K., Saito, Y., Iijima, T., Ito, H., & Murakami, M. (2006). Regulatory role of neuron-restrictive silencing factor in expression of TRPC1. Biochemical and biophysical research communications, 351(3), 764-770. https://doi.org/10.1016/j.bbrc.2006.10.107