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 journalArticle

25 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 languageEnglish
Pages (from-to)1299-1305
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume338
Issue number2
DOIs
Publication statusPublished - 16-12-2005

Fingerprint

Calcineurin
Cardiomegaly
Calmodulin
Tacrolimus
Atrial Natriuretic Factor
Cardiac Myocytes
Gene expression
Gene Expression
Myosin Heavy Chains
Transgenic Mice
Rats
Up-Regulation
Genes
Chemical activation
Body Weight
Parturition

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Obata, Koji ; Nagata, Kohzo ; Iwase, Mitsunori ; Odashima, Mari ; Nagasaka, Tetsuro ; Izawa, Hideo ; Murohara, Toyoaki ; Yamada, Yoshiji ; Yokota, Mitsuhiro. / Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 338, No. 2. pp. 1299-1305.
@article{9e91989874034753965cfe35abc722a5,
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",
year = "2005",
month = "12",
day = "16",
doi = "10.1016/j.bbrc.2005.10.083",
language = "English",
volume = "338",
pages = "1299--1305",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

Obata, K, Nagata, K, Iwase, M, Odashima, M, Nagasaka, T, Izawa, H, Murohara, T, Yamada, Y & Yokota, M 2005, 'Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway', Biochemical and Biophysical Research Communications, vol. 338, no. 2, pp. 1299-1305. https://doi.org/10.1016/j.bbrc.2005.10.083

Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway. / Obata, Koji; Nagata, Kohzo; Iwase, Mitsunori; Odashima, Mari; Nagasaka, Tetsuro; Izawa, Hideo; Murohara, Toyoaki; Yamada, Yoshiji; Yokota, Mitsuhiro.

In: Biochemical and Biophysical Research Communications, Vol. 338, No. 2, 16.12.2005, p. 1299-1305.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway

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.

UR - http://www.scopus.com/inward/record.url?scp=27744588009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744588009&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2005.10.083

DO - 10.1016/j.bbrc.2005.10.083

M3 - Article

C2 - 16256941

AN - SCOPUS:27744588009

VL - 338

SP - 1299

EP - 1305

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -