Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction
Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction
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DOI：
10.1016/s0002-9440(10)61735-x
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发表时间：
2001-08-01
影响因子：
6
通讯作者：
Hai, T
中科院分区：
文献类型：
--
作者：
Okamoto, Y;Chaves, A;Hai, T
转录激活因子3（ATF 3）是CREB/ATF转录因子家族的成员。以前，我们证明了ATF 3基因的表达是由许多应激信号诱导的。在这份报告中，我们证明了ATF 3的表达诱导心肌缺血再灌注（缺血再灌注）在培养的细胞和动物模型。在α-肌球蛋白重链启动子控制下表达ATF 3的转基因小鼠具有心房增大、心房和心室肥大。光镜下见心肌细胞变性、纤维化。在功能上，转基因心脏具有降低的收缩性和异常传导。有趣的是，在这些转基因心脏中，sorcin的表达增加，sorcin是一种其产物抑制肌浆网钙释放的基因。综上所述，我们的研究结果表明，ATF 3，一种应激诱导基因，在心脏中的表达导致基因表达改变和心脏功能受损。
Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha -myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function.