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

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 Ca{sup 2+} channel (SOCC)-mediated Ca{sup 2+} 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.

Authors:
 [1];  [1];  [1];  [2];  [3];  [4];  [5];  [1];  [2];  [6];  [7];  [8];  [8];  [5];  [1];  [9]
  1. Second Department of Internal Medicine, Akita University School of Medicine, Akita (Japan)
  2. Department of Pathology, Tohoku University School of Medicine, Sendai (Japan)
  3. Center for Experimental Animal Science, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)
  4. Department of Cell Physiology, Nagoya University Graduate School of Medicine, Tsuruma-cho, Shouwa, Nagoya (Japan)
  5. Department of Pharmacology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543 (Japan)
  6. Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto (Japan)
  7. Institute for Drug Discovery Research, Astellas Pharmaceutical Co. Ltd, Ibaraki (Japan)
  8. First Department of Internal Medicine, Nara Medical University, Nara (Japan)
  9. Department of Pharmacology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010-8543 (Japan). E-mail: mmura0123@hotmail.co.jp
Publication Date:
OSTI Identifier:
20857932
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 351; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.10.107; PII: S0006-291X(06)02374-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CALCIUM IONS; DNA; GENES; HEART; NERVE CELLS; POLYMERASE CHAIN REACTION; PROMOTERS; RECEPTORS; TRANSCRIPTION; TRANSGENIC MICE

Citation Formats

Ohba, Takayoshi, Watanabe, Hiroyuki, Takahashi, Yoichiro, Suzuki, Takashi, Miyoshi, Ichiro, Nakayama, Shinnsuke, Satoh, Eisaku, Iino, Kenji, Sasano, Hironobu, Mori, Yasuo, Kuromitsu, Sadao, Imagawa, Keiichi, Saito, Yoshihiko, Iijima, Toshihiko, Ito, Hiroshi, and Murakami, Manabu. Regulatory role of neuron-restrictive silencing factor in expression of TRPC1. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.10.107.
Ohba, Takayoshi, Watanabe, Hiroyuki, Takahashi, Yoichiro, Suzuki, Takashi, Miyoshi, Ichiro, Nakayama, Shinnsuke, Satoh, Eisaku, Iino, Kenji, Sasano, Hironobu, Mori, Yasuo, Kuromitsu, Sadao, Imagawa, Keiichi, Saito, Yoshihiko, Iijima, Toshihiko, Ito, Hiroshi, & Murakami, Manabu. Regulatory role of neuron-restrictive silencing factor in expression of TRPC1. United States. doi:10.1016/j.bbrc.2006.10.107.
Ohba, Takayoshi, Watanabe, Hiroyuki, Takahashi, Yoichiro, Suzuki, Takashi, Miyoshi, Ichiro, Nakayama, Shinnsuke, Satoh, Eisaku, Iino, Kenji, Sasano, Hironobu, Mori, Yasuo, Kuromitsu, Sadao, Imagawa, Keiichi, Saito, Yoshihiko, Iijima, Toshihiko, Ito, Hiroshi, and Murakami, Manabu. Fri . "Regulatory role of neuron-restrictive silencing factor in expression of TRPC1". United States. doi:10.1016/j.bbrc.2006.10.107.
@article{osti_20857932,
title = {Regulatory role of neuron-restrictive silencing factor in expression of TRPC1},
author = {Ohba, Takayoshi and Watanabe, Hiroyuki and Takahashi, Yoichiro and Suzuki, Takashi and Miyoshi, Ichiro and Nakayama, Shinnsuke and Satoh, Eisaku and Iino, Kenji and Sasano, Hironobu and Mori, Yasuo and Kuromitsu, Sadao and Imagawa, Keiichi and Saito, Yoshihiko and Iijima, Toshihiko and Ito, Hiroshi and Murakami, Manabu},
abstractNote = {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 Ca{sup 2+} channel (SOCC)-mediated Ca{sup 2+} 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.},
doi = {10.1016/j.bbrc.2006.10.107},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 351,
place = {United States},
year = {Fri Dec 22 00:00:00 EST 2006},
month = {Fri Dec 22 00:00:00 EST 2006}
}