Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway

被引：31
作者：
Obata, K
Nagata, K
Iwase, M
Odashima, M
Nagasaka, T
Izawa, H
Murohara, T
Yamada, Y
Yokota, M [1 ]
机构：
[1] Nagoya Univ, Sch Med, Dept Cardiovasc Genome Sci, Nagoya, Aichi 466, Japan
[2] Nagoya Univ, Sch Hlth Sci, Dept Med Technol, Nagoya, Aichi, Japan
[3] Nagoya Univ, Grad Sch Med, Dept Clin Pathophysiol, Nagoya, Aichi, Japan
[4] Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi, Japan
[5] Mie Univ, Life Sci Res Ctr, Dept Human Funct Genom, Tsu, Mie 514, Japan
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 338卷 / 02期
关键词：
calmodulin; calcineurin; FK506; cardiac hypertrophy; transgenic mouse;
D O I：
10.1016/j.bbrc.2005.10.083
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：
The possible role of calcineurin in cardiac hypertrophy induced by calmodulin (CaM) overexpression in the heart was investigated. CaM transgenic (CaM-TG) mice developed marked cardiac hypertrophy and exhibited up-regulation of atrial natriuretic factor (ANF) and P-myosin heavy chain gene expression in the heart during the first 2 weeks after birth. The activity of calcineurin in the heart was also significantly increased in CaM-TG mice compared with wild-type littermates. Treatment of CaM-TG mice with the calcineurin inhibitor FK506 (1 mg/kg per day) prevented the increase in the heart-to-body weight ratio as well as that in cardiomyocyte width. FK506 also inhibited the induction of fetal-type cardiac gene expression in CaM-TG mice. Overexpression of CaM in cultured rat cardiomyocytes activated the ANF gene promoter in a manner sensitive to FK506. Activation of a calcineurin-dependent pathway thus contributes to the development of cardiac hypertrophy induced by CaM overexpression in the heart. (c) 2005 Elsevier Inc. All rights reserved.
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收藏
页码：1299 / 1305
页数：7
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