title: Nm23-M5 mediates round and elongated spermatid survival by regulating GPX-5 levels.
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.
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Seong-Keon
authors.initials: SK
authors.lastname: Cho
authors.forename: Kyu-Chan
authors.initials: KC
authors.lastname: Hwang
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Soo-Bong
authors.initials: SB
authors.lastname: Park
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Hwang
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: 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
chemical_list: D017931:DNA Primers; D054778:NM23 Nucleoside Diphosphate Kinases; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; C080439:selenium-independent glutathione peroxidase