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

被引：23
作者：
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
机构：
[1] Akita Univ, Sch Med, Dept Pharmacol, Akita 0108543, Japan
[2] Akita Univ, Sch Med, Dept Internal Med 2, Akita 010, Japan
[3] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan
[4] Nagoya City Univ, Grad Sch Med Sci, Ctr Expt Anim Sci, Nagoya, Aichi, Japan
[5] Kyoto Univ, Grad Sch Engn, Mol Biol Lab, Dept Synth Chem & Biol Chem, Kyoto, Japan
[6] Astellas Pharmaceut Co Ltd, Inst Drug Discovery Res, Ibaraki, Japan
[7] Nara Med Univ, Dept Internal Med 1, Nara, Japan
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2006年 / 351卷 / 03期
基金：
日本学术振兴会;
关键词：
NRSF; TRPC1; SOC;
D O I：
10.1016/j.bbrc.2006.10.107
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (c) 2006 Elsevier Inc. All rights reserved.
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收藏
页码：764 / 770
页数：7
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