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

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28 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

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    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, 338(2), 1299-1305. https://doi.org/10.1016/j.bbrc.2005.10.083