Nm23-M5 mediates round and elongated spermatid survival by regulating GPX-5 levels |
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Authors: | Yun-Jung Choi Seong-Keon Cho Kyu-Chan Hwang Jae-Hwan kim Seongsoo Hwang |
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Affiliation: | a Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea b CHO-A Biotechnology Research Institute, CHO-A Pharmaceutical Co., Ltd., Seoul 150-992, Republic of Korea c CHA Stem Cell Institute, Graduate School of Life Science and Biotechnology, Pochon CHA University, Seoul 135-907, South Korea d Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, South Korea |
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Abstract: | 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. |
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