Nm23-M5 mediates round and elongated spermatid survival by regulating GPX-5 levels.
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.
Choi
Yun-Jung
YJ
Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
Cho
Seong-Keon
SK
Hwang
Kyu-Chan
KC
Park
Chankyu
C
Kim
Jae-Hwan
JH
Park
Soo-Bong
SB
Hwang
Seongsoo
S
Kim
Jin-Hoi
JH
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D016466:CHO Cells; D002470:Cell Survival / Q000502:physiology*; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013087:Spermatids / Q000166:cytology*; D013091:Spermatogenesis / Q000235:genetics
D017931:DNA Primers; D054778:NM23 Nucleoside Diphosphate Kinases; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; C080439:selenium-independent glutathione peroxidase