Protective role of Nd1 in doxorubicin-induced cardiotoxicity
Protective role of Nd1 in doxorubicin-induced cardiotoxicity
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DOI：
10.1016/j.cardiores.2004.07.009
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发表时间：
2004-11-01
影响因子：
10.8
通讯作者：
Hatano, M
中科院分区：
文献类型：
--
作者：
Fujimura, L;Matsudo, Y;Hatano, M
目的：ND1基因编码一种新的海藻蛋白家族蛋白，在小鼠组织中广泛表达。体外研究表明，ND1蛋白与肌动蛋白细丝结合，起到细胞骨架稳定剂的作用。为了阐明NDL在体内的生理功能，我们建立了ND1缺失(ND1-/-)小鼠。结果：ND1-/-小鼠存活，出生后未见大体解剖异常。当小鼠胚胎成纤维细胞在含有D或阿霉素的松弛液中培养时，ND1/-细胞培养中的凋亡细胞数多于野生型细胞培养中的细胞。此外，ND1-/-小鼠对阿霉素诱导的心脏毒性反应敏感，心肌细胞凋亡率增加。结论：虽然ND1基因对于正常小鼠的发育是必不可少的，但ND1基因对阿霉素诱导的心脏毒性反应具有保护作用。(C)2004年欧洲心脏病学会。爱思唯尔出版，版权所有。
Objective: The Nd1 gene, encods a novel kelch family protein, is expressed ubiquitously in mouse tissues. In vitro studies suggest that Nd1 protein, which binds to actin filaments, functions as a cytoskeletal stabilizer. In order to elucidate a physiological function of Ndl in vivo, we generated Nd1-deficient (Nd1-/-) mice.Methods: We developed Nd1-/- mice by standard gene targeting technique. Cardiac function was studied in wild type and Nd1-/- mice.Results: Nd1-/- mice were viable and no gross anatomical abnormality was observed after birth. When mouse embryonic fibroblasts were cultured in the presence of cytochalas in D or doxorubicin, the number of apoptotic cells in the Nd1-/- cell culture was larger that that in the wild-type cell culture. Furthermore, Nd1-/- mice were sensitive to doxombicin-induced cardiotoxicity with increased numbers of cardiomyocytes apoptosis.Conclusions: Although Nd1 is dispensable for normal mice development, Nd1 plays a protective role in doxorubicin-induced cardiotoxic responses. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.