Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility
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,...
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description | 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. |
doi_str_mv | 10.1038/srep23171 |
format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep23171</identifier><identifier>PMID: 27003159</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 14/63 ; 631/136/1425 ; 631/80/474/2085 ; 82/58 ; Animals ; Autoantigens - genetics ; Autoantigens - metabolism ; Fertility ; Gene Expression Regulation ; Gene Knockout Techniques ; Humanities and Social Sciences ; Male ; Mice ; multidisciplinary ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Oxidative Stress ; Proteasome Endopeptidase Complex - genetics ; Proteasome Endopeptidase Complex - metabolism ; Science ; Science (multidisciplinary) ; Sperm Motility ; Spermatozoa - metabolism ; Spermatozoa - physiology ; Up-Regulation</subject><ispartof>Scientific reports, 2016-03, Vol.6 (1), p.23171-23171, Article 23171</ispartof><rights>The Author(s) 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-3350fcad61a9b9c3d547a7b141341769d8eac8d76d335f01474bc6c2d47f19ea3</citedby><cites>FETCH-LOGICAL-c454t-3350fcad61a9b9c3d547a7b141341769d8eac8d76d335f01474bc6c2d47f19ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802386/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802386/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27003159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Lin</creatorcontrib><creatorcontrib>Haratake, Kousuke</creatorcontrib><creatorcontrib>Miyahara, Hatsumi</creatorcontrib><creatorcontrib>Chiba, Tomoki</creatorcontrib><title>Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>13/51</subject><subject>14/63</subject><subject>631/136/1425</subject><subject>631/80/474/2085</subject><subject>82/58</subject><subject>Animals</subject><subject>Autoantigens - genetics</subject><subject>Autoantigens - metabolism</subject><subject>Fertility</subject><subject>Gene Expression Regulation</subject><subject>Gene Knockout Techniques</subject><subject>Humanities and Social Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Oxidative Stress</subject><subject>Proteasome Endopeptidase Complex - genetics</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sperm Motility</subject><subject>Spermatozoa - metabolism</subject><subject>Spermatozoa - physiology</subject><subject>Up-Regulation</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNptkd1KxDAQhYMo7qJe-ALSSxVX89emvREW8Q8WFNTrME3SNUvb1KQV9rl8D5_JyOqygrnJTObjTDgHoUOCzwlm-UXwpqOMCLKFxhTzdEIZpdsb9QgdhLDA8aS04KTYRSMqMGYkLcbo6dG73kBwjUlA9fYdeufDWfI4pfnnRwKt_i4xPku6GpaJbbUNnWkDlLVJvKtNiG9JA7GrjO9tbfvlPtqpoA7m4OfeQy83189Xd5PZw-391XQ2UTzl_YSxFFcKdEagKAvFdMoFiJJwwjgRWaFzAyrXItORrDDhgpcqU1RzUZHCANtDlyvdbigbo5Vpew-17LxtwC-lAyv_Tlr7KufuXfIcU5ZnUeD4R8C7t8GEXjY2KFPX0Bo3BEmESDOGBcsjerJClXchWl6t1xAsv3OQ6xwie7T5rzX563oETldAiKN2brxcuMG30at_1L4AiliSPw</recordid><startdate>20160322</startdate><enddate>20160322</enddate><creator>Huang, Lin</creator><creator>Haratake, Kousuke</creator><creator>Miyahara, Hatsumi</creator><creator>Chiba, Tomoki</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160322</creationdate><title>Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility</title><author>Huang, Lin ; Haratake, Kousuke ; Miyahara, Hatsumi ; Chiba, Tomoki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-3350fcad61a9b9c3d547a7b141341769d8eac8d76d335f01474bc6c2d47f19ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/51</topic><topic>14/63</topic><topic>631/136/1425</topic><topic>631/80/474/2085</topic><topic>82/58</topic><topic>Animals</topic><topic>Autoantigens - genetics</topic><topic>Autoantigens - metabolism</topic><topic>Fertility</topic><topic>Gene Expression Regulation</topic><topic>Gene Knockout Techniques</topic><topic>Humanities and Social Sciences</topic><topic>Male</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Oxidative Stress</topic><topic>Proteasome Endopeptidase Complex - genetics</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sperm Motility</topic><topic>Spermatozoa - metabolism</topic><topic>Spermatozoa - physiology</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Lin</creatorcontrib><creatorcontrib>Haratake, Kousuke</creatorcontrib><creatorcontrib>Miyahara, Hatsumi</creatorcontrib><creatorcontrib>Chiba, Tomoki</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Lin</au><au>Haratake, Kousuke</au><au>Miyahara, Hatsumi</au><au>Chiba, Tomoki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-03-22</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>23171</spage><epage>23171</epage><pages>23171-23171</pages><artnum>23171</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27003159</pmid><doi>10.1038/srep23171</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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source | Nature Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
subjects | 13/51 14/63 631/136/1425 631/80/474/2085 82/58 Animals Autoantigens - genetics Autoantigens - metabolism Fertility Gene Expression Regulation Gene Knockout Techniques Humanities and Social Sciences Male Mice multidisciplinary Nuclear Proteins - genetics Nuclear Proteins - metabolism Oxidative Stress Proteasome Endopeptidase Complex - genetics Proteasome Endopeptidase Complex - metabolism Science Science (multidisciplinary) Sperm Motility Spermatozoa - metabolism Spermatozoa - physiology Up-Regulation |
title | Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility |
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