SUMO1 promotes Aβ production via the modulation of autophagy
Autophagy is one of the main mechanisms in the pathophysiology of neurodegenerative disease. The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-β (Aβ) production. Previously, we reported that SUMO1 (small ubiquitin-like modifier 1) increases Aβ levels. In th...
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| Veröffentlicht in: | Autophagy 2015-01, Vol.11 (1), p.100-112 |
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| creator | Cho, Sun-Jung Yun, Sang-Moon Jo, Chulman Lee, Dae-hoon Choi, Ki Ju Song, Jae Chun Park, Sang Ick Kim, You-Jin Koh, Young Ho |
| description | Autophagy is one of the main mechanisms in the pathophysiology of neurodegenerative disease. The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-β (Aβ) production. Previously, we reported that SUMO1 (small ubiquitin-like modifier 1) increases Aβ levels. In this study, we explored the mechanisms underlying this. We investigated whether AV formation is necessary for Aβ production by SUMO1. Overexpression of SUMO1 increased autophagic activation, inducing the formation of LC3-II-positive AVs in neuroglioma H4 cells. Consistently, autophagic activation was decreased by the depletion of SUMO1 with small hairpin RNA (shRNA) in H4 cells. The SUMO1-mediated increase in Aβ was reduced by the autophagy inhibitors (3-methyladenine or wortmannin) or genetic inhibitors (siRNA targeting ATG5, ATG7, ATG12, or HIF1A), respectively. Accumulation of SUMO1, ATG12, and LC3 was seen in amyloid precursor protein transgenic mice. Our results suggest that SUMO1 accelerates the accumulation of AVs and promotes Aβ production, which is a key mechanism for understanding the AV-mediated pathophysiology of Alzheimer disease. |
| doi_str_mv | 10.4161/15548627.2014.984283 |
| format | Article |
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The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-β (Aβ) production. Previously, we reported that SUMO1 (small ubiquitin-like modifier 1) increases Aβ levels. In this study, we explored the mechanisms underlying this. We investigated whether AV formation is necessary for Aβ production by SUMO1. Overexpression of SUMO1 increased autophagic activation, inducing the formation of LC3-II-positive AVs in neuroglioma H4 cells. Consistently, autophagic activation was decreased by the depletion of SUMO1 with small hairpin RNA (shRNA) in H4 cells. The SUMO1-mediated increase in Aβ was reduced by the autophagy inhibitors (3-methyladenine or wortmannin) or genetic inhibitors (siRNA targeting ATG5, ATG7, ATG12, or HIF1A), respectively. Accumulation of SUMO1, ATG12, and LC3 was seen in amyloid precursor protein transgenic mice. Our results suggest that SUMO1 accelerates the accumulation of AVs and promotes Aβ production, which is a key mechanism for understanding the AV-mediated pathophysiology of Alzheimer disease.</description><identifier>ISSN: 1554-8627</identifier><identifier>EISSN: 1554-8635</identifier><identifier>DOI: 10.4161/15548627.2014.984283</identifier><identifier>PMID: 25484073</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>AD, Alzheimer disease ; Alzheimer disease ; amyloid ; Amyloid beta-Peptides - metabolism ; Amyloid beta-Peptides - ultrastructure ; Animals ; Apoptosis Regulatory Proteins - metabolism ; ATG, autophagy-related ; ATG12 ; Autophagy ; AV, autophagic vacuole ; Aβ, amyloid-β ; Basic Research Papers ; Beclin-1 ; Brain - metabolism ; Cell Line, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; LC3 ; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3 ; MDC, monodansylcadaverine ; Mice, Transgenic ; Microtubule-Associated Proteins - metabolism ; Plaque, Amyloid - metabolism ; RNA, Small Interfering - metabolism ; shRNA, small hairpin RNA ; SUMO-1 Protein - metabolism ; SUMO1 ; SUMO1, small ubiquitin-like modifier 1 ; TEM, transmission electron microscopy, Tg, transgenic ; Transfection ; Up-Regulation</subject><ispartof>Autophagy, 2015-01, Vol.11 (1), p.100-112</ispartof><rights>2015 Taylor & Francis Group, LLC 2015</rights><rights>2015 Taylor & Francis Group, LLC 2015 Taylor & Francis Group, LLC</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-193fc5633f7021468ee8e7e58796ebbd621857f0e8de37a402314433a214ce9f3</citedby><cites>FETCH-LOGICAL-c464t-193fc5633f7021468ee8e7e58796ebbd621857f0e8de37a402314433a214ce9f3</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/PMC4502770/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502770/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25484073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Sun-Jung</creatorcontrib><creatorcontrib>Yun, Sang-Moon</creatorcontrib><creatorcontrib>Jo, Chulman</creatorcontrib><creatorcontrib>Lee, Dae-hoon</creatorcontrib><creatorcontrib>Choi, Ki Ju</creatorcontrib><creatorcontrib>Song, Jae Chun</creatorcontrib><creatorcontrib>Park, Sang Ick</creatorcontrib><creatorcontrib>Kim, You-Jin</creatorcontrib><creatorcontrib>Koh, Young Ho</creatorcontrib><title>SUMO1 promotes Aβ production via the modulation of autophagy</title><title>Autophagy</title><addtitle>Autophagy</addtitle><description>Autophagy is one of the main mechanisms in the pathophysiology of neurodegenerative disease. The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-β (Aβ) production. Previously, we reported that SUMO1 (small ubiquitin-like modifier 1) increases Aβ levels. In this study, we explored the mechanisms underlying this. We investigated whether AV formation is necessary for Aβ production by SUMO1. Overexpression of SUMO1 increased autophagic activation, inducing the formation of LC3-II-positive AVs in neuroglioma H4 cells. Consistently, autophagic activation was decreased by the depletion of SUMO1 with small hairpin RNA (shRNA) in H4 cells. The SUMO1-mediated increase in Aβ was reduced by the autophagy inhibitors (3-methyladenine or wortmannin) or genetic inhibitors (siRNA targeting ATG5, ATG7, ATG12, or HIF1A), respectively. Accumulation of SUMO1, ATG12, and LC3 was seen in amyloid precursor protein transgenic mice. Our results suggest that SUMO1 accelerates the accumulation of AVs and promotes Aβ production, which is a key mechanism for understanding the AV-mediated pathophysiology of Alzheimer disease.</description><subject>AD, Alzheimer disease</subject><subject>Alzheimer disease</subject><subject>amyloid</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-Peptides - ultrastructure</subject><subject>Animals</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>ATG, autophagy-related</subject><subject>ATG12</subject><subject>Autophagy</subject><subject>AV, autophagic vacuole</subject><subject>Aβ, amyloid-β</subject><subject>Basic Research Papers</subject><subject>Beclin-1</subject><subject>Brain - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>LC3</subject><subject>MAP1LC3/LC3, microtubule-associated protein 1 light chain 3</subject><subject>MDC, monodansylcadaverine</subject><subject>Mice, Transgenic</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Plaque, Amyloid - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>shRNA, small hairpin RNA</subject><subject>SUMO-1 Protein - metabolism</subject><subject>SUMO1</subject><subject>SUMO1, small ubiquitin-like modifier 1</subject><subject>TEM, transmission electron microscopy, Tg, transgenic</subject><subject>Transfection</subject><subject>Up-Regulation</subject><issn>1554-8627</issn><issn>1554-8635</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtOwzAURS0EouWzA4QyZNLiv50BIIT4SUUdAGPLTZ7boCQudgLqtlgIayKltIIJI9vX9973dBA6InjIiSSnRAiuJVVDigkfpppTzbZQfykPtGRie3Onqof2YnzBmEmd0l3Uo12UY8X66Ozx-WFMknnwlW8gJpefH8tH3mZN4evkrbBJM4Ok6pTSfkveJbZt_Hxmp4sDtONsGeHw59xHzzfXT1d3g9H49v7qcjTIuOTNgKTMZUIy5hSmhEsNoEGB0CqVMJnkkhItlMOgc2DKckwZ4Zwx25kzSB3bR-er3nk7qSDPoG6CLc08FJUNC-NtYf7-1MXMTP2b4QJTpXBXcPJTEPxrC7ExVREzKEtbg2-jIVIoRhnlorPylTULPsYAbjOGYLMkb9bkzZK8WZHvYse_V9yE1qg7w8XKUNTOh8q--1DmprGL0gcXbJ0V0bB_R3wBd3WS4g</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Cho, Sun-Jung</creator><creator>Yun, Sang-Moon</creator><creator>Jo, Chulman</creator><creator>Lee, Dae-hoon</creator><creator>Choi, Ki Ju</creator><creator>Song, Jae Chun</creator><creator>Park, Sang Ick</creator><creator>Kim, You-Jin</creator><creator>Koh, Young Ho</creator><general>Taylor & Francis</general><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>20150101</creationdate><title>SUMO1 promotes Aβ production via the modulation of autophagy</title><author>Cho, Sun-Jung ; Yun, Sang-Moon ; Jo, Chulman ; Lee, Dae-hoon ; Choi, Ki Ju ; Song, Jae Chun ; Park, Sang Ick ; Kim, You-Jin ; Koh, Young Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-193fc5633f7021468ee8e7e58796ebbd621857f0e8de37a402314433a214ce9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>AD, Alzheimer disease</topic><topic>Alzheimer disease</topic><topic>amyloid</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-Peptides - ultrastructure</topic><topic>Animals</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>ATG, autophagy-related</topic><topic>ATG12</topic><topic>Autophagy</topic><topic>AV, autophagic vacuole</topic><topic>Aβ, amyloid-β</topic><topic>Basic Research Papers</topic><topic>Beclin-1</topic><topic>Brain - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>LC3</topic><topic>MAP1LC3/LC3, microtubule-associated protein 1 light chain 3</topic><topic>MDC, monodansylcadaverine</topic><topic>Mice, Transgenic</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Plaque, Amyloid - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>shRNA, small hairpin RNA</topic><topic>SUMO-1 Protein - metabolism</topic><topic>SUMO1</topic><topic>SUMO1, small ubiquitin-like modifier 1</topic><topic>TEM, transmission electron microscopy, Tg, transgenic</topic><topic>Transfection</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cho, Sun-Jung</creatorcontrib><creatorcontrib>Yun, Sang-Moon</creatorcontrib><creatorcontrib>Jo, Chulman</creatorcontrib><creatorcontrib>Lee, Dae-hoon</creatorcontrib><creatorcontrib>Choi, Ki Ju</creatorcontrib><creatorcontrib>Song, Jae Chun</creatorcontrib><creatorcontrib>Park, Sang Ick</creatorcontrib><creatorcontrib>Kim, You-Jin</creatorcontrib><creatorcontrib>Koh, Young Ho</creatorcontrib><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>Autophagy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Sun-Jung</au><au>Yun, Sang-Moon</au><au>Jo, Chulman</au><au>Lee, Dae-hoon</au><au>Choi, Ki Ju</au><au>Song, Jae Chun</au><au>Park, Sang Ick</au><au>Kim, You-Jin</au><au>Koh, Young Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SUMO1 promotes Aβ production via the modulation of autophagy</atitle><jtitle>Autophagy</jtitle><addtitle>Autophagy</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>11</volume><issue>1</issue><spage>100</spage><epage>112</epage><pages>100-112</pages><issn>1554-8627</issn><eissn>1554-8635</eissn><abstract>Autophagy is one of the main mechanisms in the pathophysiology of neurodegenerative disease. The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-β (Aβ) production. Previously, we reported that SUMO1 (small ubiquitin-like modifier 1) increases Aβ levels. In this study, we explored the mechanisms underlying this. We investigated whether AV formation is necessary for Aβ production by SUMO1. Overexpression of SUMO1 increased autophagic activation, inducing the formation of LC3-II-positive AVs in neuroglioma H4 cells. Consistently, autophagic activation was decreased by the depletion of SUMO1 with small hairpin RNA (shRNA) in H4 cells. The SUMO1-mediated increase in Aβ was reduced by the autophagy inhibitors (3-methyladenine or wortmannin) or genetic inhibitors (siRNA targeting ATG5, ATG7, ATG12, or HIF1A), respectively. Accumulation of SUMO1, ATG12, and LC3 was seen in amyloid precursor protein transgenic mice. Our results suggest that SUMO1 accelerates the accumulation of AVs and promotes Aβ production, which is a key mechanism for understanding the AV-mediated pathophysiology of Alzheimer disease.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>25484073</pmid><doi>10.4161/15548627.2014.984283</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | AD, Alzheimer disease Alzheimer disease amyloid Amyloid beta-Peptides - metabolism Amyloid beta-Peptides - ultrastructure Animals Apoptosis Regulatory Proteins - metabolism ATG, autophagy-related ATG12 Autophagy AV, autophagic vacuole Aβ, amyloid-β Basic Research Papers Beclin-1 Brain - metabolism Cell Line, Tumor Hypoxia-Inducible Factor 1, alpha Subunit - metabolism LC3 MAP1LC3/LC3, microtubule-associated protein 1 light chain 3 MDC, monodansylcadaverine Mice, Transgenic Microtubule-Associated Proteins - metabolism Plaque, Amyloid - metabolism RNA, Small Interfering - metabolism shRNA, small hairpin RNA SUMO-1 Protein - metabolism SUMO1 SUMO1, small ubiquitin-like modifier 1 TEM, transmission electron microscopy, Tg, transgenic Transfection Up-Regulation |
| title | SUMO1 promotes Aβ production via the modulation of autophagy |
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