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

研究成果: Article査読

29 被引用数 (Scopus)


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.

ジャーナルBiochemical and Biophysical Research Communications
出版ステータスPublished - 16-12-2005

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学


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