Store-operated Ca entry regulates the cardiac hypertrophic response

钙库操纵的钙进入调节心脏肥厚反应

• 批准号: 17590700
• 负责人: WATANABE Hiroyuki
• 金额: $ 2.24万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590700/
• 关键词: TRP channel; Calcium; cardiac hypertrophy; molecular biology; electrophysiology; sarcoplasmic reticulum; BNP

The importance of Ca entry in the cardiac hypertrophic response is well documented, but the actual Ca entry channels remain unknown. Transient receptor potential (TRP) proteins are thought to form Ca entry channels that are involved in the proliferation various cells. The purpose of this study was to explore the potential involvement of TRP channels in the development of cardiac hypertrophy. EMSA revealed an interaction between NRSF (neuron restrictive silence factor) and a NRSE-like sequence in TRPC1 genomic DNA. We found that TRPC1 was up-regulated in dnNRSF-Tg mice heart which mimick dilated cardiomyopathy. These results suggest that TRPC1 has the character of fetal cardiac gene and reexpresses in the cardiomyopathy. Although TRPs C1, C3, C5, and C6 were constitutively expressed, only TRPC1 expression was significantly increased in the hearts of abdominal aortic-banded rats compared to sham-operated rats. Using primary cultures of neonatal rat cardiomyocytes, we detected increases i … More n the expression of TRPC1, brain natriuretic peptide (BNP), and atrial natriuretic factor (ANF), as well as increases in store-operated Ca entry (SOCE) and cell surface area, following endothelin-1 (ET-1) treatment. Silencing of the TRPC1 gene via small interfering RNA (siRNA) attenuated SOCE and prevented ET-1-, angiotensin-II (AT II)-, and phenylephrine (PE)-induced cardiac hypertrophy. In HEK 293T cells, overexpression of TRPC1 augmented SOCE, leading to an increase in nuclear factor of activated T cells (NFAT) promoter activity, while co-transfection with dominant-negative forms of TRPC1 suppressed it. Mreover, we examined the involvement of TRPC1 in the vascular smooth muscle cell hypertrophy. We demonstrate Ang II and subsequent NF-kappaB activation induces hCASMC hypertrophy through an enhancement of TRPC1 expression. In conclusion, TRPC1 functions in Ca influx, and its upregulation is involved in the development of cardiac and vascular hypertrophy ; moreover, it plays an important role in the regulation of the signaling pathways that govern cardiac and vascular hypertrophy. Less

钙离子进入心脏肥厚反应的重要性已被充分证明，但实际的钙离子进入通道尚不清楚。瞬时受体电位（TRP）蛋白被认为形成钙离子进入通道，参与各种细胞的增殖。本研究的目的是探讨TRP通道在心肌肥厚发展中的潜在参与。EMSA发现NRSF（神经元限制性沉默因子）与TRPC1基因组DNA中的nrse样序列之间存在相互作用。我们发现TRPC1在模拟扩张型心肌病的dnNRSF-Tg小鼠心脏中表达上调。提示TRPC1具有胎心基因的特征，并在心肌病中重新表达。虽然TRPs C1、C3、C5和C6组成性表达，但与假手术大鼠相比，腹主动脉束带大鼠心脏中只有TRPC1表达显著增加。利用原代培养的新生大鼠心肌细胞，我们检测到内皮素-1 （ET-1）处理后，TRPC1、脑钠肽（BNP）和心房钠素因子（ANF）的表达增加，储运钙进入（SOCE）和细胞表面积增加。通过小干扰RNA （siRNA）沉默TRPC1基因可减轻SOCE，并阻止ET-1-、血管紧张素-II (AT II)-和苯肾上腺素（PE）诱导的心肌肥厚。在HEK 293T细胞中，TRPC1的过表达增强了SOCE，导致活化T细胞核因子（NFAT）启动子活性的增加，而与TRPC1的显性阴性形式共转染则抑制了SOCE。此外，我们还研究了TRPC1在血管平滑肌细胞肥大中的作用。我们证明Ang II和随后的NF-kappaB激活通过增强TRPC1表达诱导hCASMC肥大。综上所述，TRPC1在Ca内流中起作用，其上调参与了心肌和血管肥大的发生；此外，它在调控心脏和血管肥大的信号通路中起重要作用。少

项目成果

Upregulation of TRPC1 in the development of cardiac hypertrophy

• DOI: 10.1016/j.yjmcc.2006.10.020
• 发表时间: 2007-03-01
• 期刊: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
• 影响因子: 5
• 作者: Ohba, Takayoshi;Watanabe, Hiroyuki;Ito, Hiroshi
• 通讯作者: Ito, Hiroshi

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

• DOI: 10.1016/j.bbrc.2006.10.107
• 发表时间: 2006-12-22
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Ohba, Takayoshi;Watanabe, Hiroyuki;Murakami, Manabu
• 通讯作者: Murakami, Manabu

Annual Review ardiology in 2007

2007年心脏病学年度回顾

• 发表时间: 2007
• 作者: Niizeki T;et al.;Hiroyuki WATANABE.
• 通讯作者: Hiroyuki WATANABE.

Genomic organization and functional analysis of murine PKD2L1

• DOI: 10.1074/jbc.m411496200
• 发表时间: 2005-02-18
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Murakami, M;Ohba, T;Iijima, T
• 通讯作者: Iijima, T

Essential role of the N-terminus of murine Orail in store-operated Ca^<2+>entry

小鼠 Orail N 末端在库操作 Ca^<2 > 进入中的重要作用

• 发表时间: 2007
• 期刊: Biochemical & Biophysical Research communications 356
• 作者: Takahashi;Y.;et. al.
• 通讯作者: et. al.