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Nm23‐M5 mediates round and elongated spermatid survival by regulating GPX‐5 levels
Author(s) -
Choi Yun-Jung,
Cho Seong-Keon,
Hwang Kyu-Chan,
Park Chankyu,
kim Jae-Hwan,
Park Soo-Bong,
Hwang Seongsoo,
Kim Jin-Hoi
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.03.023
Subject(s) - small hairpin rna , microbiology and biotechnology , nucleoside diphosphate kinase , spermatid , biology , northern blot , western blot , transgene , glutathione peroxidase , spermiogenesis , blot , gene , messenger rna , biochemistry , glutathione , rna , enzyme , genetics , nucleus , sperm
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.