Nm23-M5 mediates round and elongated spermatid survival by regulating GPX-5 levels
Nm23-M5 mediates round and elongated spermatid survival by regulating GPX-5 levels
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DOI：
10.1016/j.febslet.2009.03.023
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发表时间：
2009-04-17
期刊：
影响因子：
3.5
通讯作者：
Kim, Jin-Hoi
中科院分区：
文献类型：
--
作者：
Choi, Yun-Jung;Cho, Seong-Keon;Kim, Jin-Hoi
核苷二磷酸(NDP)激酶参与多种与细胞增殖、发育和分化相关的调控过程。此前，我们从小鼠中克隆了NDPK家族的一个新成员Nm23-M5，它编码一个211个氨基酸的蛋白质，与人类Nm23-H5基因有86%的同源性[Hwang，K.C.，OK，D.W.，Hong，J.C.，Kim，M.O.和Kim，J.H.(2003)小鼠精子发生和精子发生过程中小鼠Nm23-M5基因的克隆、测序和特征。生物化学。生物群落。[中英文摘要]Re.Commun.306、198-207]。为了更好地了解Nm23-M5的功能，我们在体内使用短发夹状RNA(ShRNA)敲除系统产生了Nm23-M5水平降低的转基因小鼠。Northern和Western印迹分析表明，Nm23-M5的表达显著降低。Nm23-M5 shRNA转基因小鼠的单倍体细胞数量减少。此外，抗氧化酶谷胱甘肽过氧化物酶5(GPX-5)在表达和活性水平上都受到Nm23-M5的调控。这些结果表明，Nm23-M5的表达通过增加细胞内GPX-5的水平来清除活性氧，从而在精子发生过程中发挥关键作用。(C)2009年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Nucleoside diphosphate (NDP) kinases are involved in numerous regulatory processes associated with proliferation, development, and differentiation. Previously, we cloned a new member of the NDPK family from mouse, Nm23-M5, which encodes a 211-amino acid protein and has 86% identity to the human Nm23-H5 [Hwang, K.C., Ok, D. W., Hong, J.C., Kim, M.O. and Kim, J. H. (2003) Cloning, sequencing, and characterization of the murine Nm23-M5 gene during mouse spermatogenesis and spermiogenesis. Biochem. Biophys. Res. Commun. 306, 198-207]. To better understand Nm23-M5 function, we generated transgenic mice with reduced Nm23-M5 levels in vivo using a short hairpin RNA (shRNA) knock-down system. Nm23-M5 expression was markedly reduced, as indicated by Northern and Western blot analysis. Nm23-M5 shRNA transgenic mice exhibited reduced numbers of haploid cells. Furthermore, the antioxidant enzyme glutathione peroxidase 5 (GPX-5) is regulated by Nm23-M5 at the level of both expression and activity. These results reveal that expression of Nm23-M5 plays a critical role in spermiogenesis by increasing the cellular levels of GPX-5 to eliminate reactive oxygen species. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.