title: Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility.
abstract: Protein degradation mediated by the proteasome is important for the protein homeostasis. Various proteasome activators, such as PA28 and PA200, regulate the proteasome function. Here we show double knockout (dKO) mice of Psme3 and Psme4 (genes for PA28γ and PA200), but not each single knockout mice, are completely infertile in male. The dKO sperms exhibited remarkable defects in motility, although most of them showed normal appearance in morphology. The proteasome activity of the mutant sperms decreased notably, and the sperms were strongly positive with ubiquitin staining. Quantitative analyses of proteins expressed in dKO sperms revealed up-regulation of several proteins involved in oxidative stress response. Furthermore, increased 8-OHdG staining was observed in dKO sperms head, suggesting defective response to oxidative damage. This report verified PA28γ and PA200 play indispensable roles in male fertility, and provides a novel insight into the role of proteasome activators in antioxidant response.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.|Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Haratake
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Miyahara
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D005298:Fertility; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D001324:Autoantigens; C099558:Ki antigen; D009687:Nuclear Proteins; C574231:Pa200 protein, mouse; D046988:Proteasome Endopeptidase Complex