Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway - PubMed (original) (raw)

. 2005 Dec 16;338(2):1299-305.

doi: 10.1016/j.bbrc.2005.10.083. Epub 2005 Oct 24.

Affiliations

• PMID: 16256941
• DOI: 10.1016/j.bbrc.2005.10.083

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

Koji Obata et al. Biochem Biophys Res Commun. 2005.

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 beta-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 (1mg/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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