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

Koji Obata; Kohzo Nagata; Mitsunori Iwase; Mari Odashima; Tetsuro Nagasaka; Hideo Izawa; Toyoaki Murohara; Yoshiji Yamada; Mitsuhiro Yokota

doi:10.1016/j.bbrc.2005.10.083

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

Koji Obata, Kohzo Nagata, Mitsunori Iwase, Mari Odashima, Tetsuro Nagasaka, Hideo Izawa, Toyoaki Murohara, Yoshiji Yamada, Mitsuhiro Yokota

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

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 β-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.

Original language	English
Pages (from-to)	1299-1305
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	338
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2005.10.083
Publication status	Published - 16-12-2005
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2005.10.083

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title = "Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway",

abstract = "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 β-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.",

author = "Koji Obata and Kohzo Nagata and Mitsunori Iwase and Mari Odashima and Tetsuro Nagasaka and Hideo Izawa and Toyoaki Murohara and Yoshiji Yamada and Mitsuhiro Yokota",

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doi = "10.1016/j.bbrc.2005.10.083",

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AU - Obata, Koji

AU - Nagata, Kohzo

AU - Iwase, Mitsunori

AU - Odashima, Mari

AU - Nagasaka, Tetsuro

AU - Izawa, Hideo

AU - Murohara, Toyoaki

AU - Yamada, Yoshiji

AU - Yokota, Mitsuhiro

PY - 2005/12/16

Y1 - 2005/12/16

N2 - 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 β-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.

AB - 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 β-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.

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

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