Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway.
Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway.
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DOI：
10.1016/j.bbrc.2005.10.083
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发表时间：
2005-12
影响因子：
3.1
通讯作者：
K. Obata;K. Nagata;M. Iwase;M. Odashima;T. Nagasaka;H. Izawa;T. Murohara;Yoshiji Yamada;M. Yokota
中科院分区：
文献类型：
--
作者：
K. Obata;K. Nagata;M. Iwase;M. Odashima;T. Nagasaka;H. Izawa;T. Murohara;Yoshiji Yamada;M. Yokota
研究了钙调磷酸酶在钙调蛋白（CaM）过度表达诱导的心肌肥厚中的可能作用。CaM转基因小鼠（CaM-TG）在出生后2周内出现明显的心肌肥厚，并表现出心钠素（ANF）和β-肌球蛋白重链基因表达的上调。与野生型同窝仔相比，CaM-TG小鼠心脏中钙调神经磷酸酶的活性也显著增加。用钙调磷酸酶抑制剂FK 506（每天1 mg/kg）治疗CaM-TG小鼠，可防止心脏与体重比以及心肌细胞宽度的增加。FK 506还抑制CaM-TG小鼠中胎儿型心脏基因表达的诱导。在培养的大鼠心肌细胞中过表达钙调素激活心钠素基因启动子的方式敏感FK 506。因此，钙调神经磷酸酶依赖性途径的激活有助于由心脏中CaM过表达诱导的心脏肥大的发展。
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 (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.