Valproic acid causes proteasomal degradation of DICER and influences miRNA expression
Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the...
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| Veröffentlicht in: | PloS one 2013-12, Vol.8 (12), p.e82895 |
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| creator | Zhang, Zhaiyi Convertini, Paolo Shen, Manli Xu, Xiu Lemoine, Frédéric de la Grange, Pierre Andres, Douglas A Stamm, Stefan |
| description | Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER. |
| doi_str_mv | 10.1371/journal.pone.0082895 |
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Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0082895</identifier><identifier>PMID: 24358235</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Apoptosis ; Arrays ; Autophagy ; Biochemistry ; Bioinformatics ; Cell death ; Cells, Cultured ; DEAD-box RNA Helicases - metabolism ; Degradation ; Dicer protein ; Epilepsy ; Extracellular signal-regulated kinase ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation - drug effects ; Genes ; Genetic aspects ; Genomes ; HEK293 Cells ; HeLa Cells ; Humans ; Kinases ; Microarray Analysis ; MicroRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Physiology ; Proteasome Endopeptidase Complex - metabolism ; Proteasomes ; Proteins ; Proteolysis - drug effects ; Ribonuclease III - metabolism ; Ribonucleic acid ; RNA ; Rodents ; Valproic acid ; Valproic Acid - pharmacology</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e82895</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Zhang et al 2013 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-967a201681ec527251106451bb2ff9223be34a98afe4ad578f69af7d971570b03</citedby><cites>FETCH-LOGICAL-c692t-967a201681ec527251106451bb2ff9223be34a98afe4ad578f69af7d971570b03</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/PMC3866160/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866160/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24358235$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pfeffer, Sebastien</contributor><creatorcontrib>Zhang, Zhaiyi</creatorcontrib><creatorcontrib>Convertini, Paolo</creatorcontrib><creatorcontrib>Shen, Manli</creatorcontrib><creatorcontrib>Xu, Xiu</creatorcontrib><creatorcontrib>Lemoine, Frédéric</creatorcontrib><creatorcontrib>de la Grange, Pierre</creatorcontrib><creatorcontrib>Andres, Douglas A</creatorcontrib><creatorcontrib>Stamm, Stefan</creatorcontrib><title>Valproic acid causes proteasomal degradation of DICER and influences miRNA expression</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.</description><subject>Acids</subject><subject>Apoptosis</subject><subject>Arrays</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Cell death</subject><subject>Cells, Cultured</subject><subject>DEAD-box RNA Helicases - metabolism</subject><subject>Degradation</subject><subject>Dicer protein</subject><subject>Epilepsy</subject><subject>Extracellular signal-regulated kinase</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinases</subject><subject>Microarray Analysis</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Physiology</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Proteasomes</subject><subject>Proteins</subject><subject>Proteolysis - drug effects</subject><subject>Ribonuclease III - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Rodents</subject><subject>Valproic acid</subject><subject>Valproic Acid - pharmacology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQLguDDjPnf9EUYxlUHFhdGd1_DbZrMZGibMWll_fZmnO4yBQXJQ8LN755cTk6WvcRojmmB3-_8EDpo5nvfmTlCksiSP8rOcUnJTBBEH5-cz7JnMe4Q4lQK8TQ7I4xySSg_z25uodkH73QO2tW5hiGamKdKbyD6Fpq8NpsANfTOd7m3-cfV8nKdQ1fnrrPNYDqd-Natvy5yc7cPJsYEPs-eWGiieTHuF9nNp8vvyy-zq-vPq-XiaqZFSfpZKQogCAuJjeakIBxjJBjHVUWsLQmhlaEMSgnWMKh5Ia0owRZ1WWBeoArRi-z1UXff-KhGR6LCTEgpBaUsEasjUXvYqX1wLYRfyoNTfwo-bBSE3unGKCCGI4wpYVwyTovK1LqoBGOCV7VlJml9GF8bqjZdmq4P0ExEpzed26qN_6kOrmNxGPfNKBD8j8HE_h8jj9QG0lTJZZ_EdOuiVgtWyPR3CJNEzf9CpVWb1umUCetSfdLwbtKQmN7c9Zv041Gtvq3_n72-nbJvT9itgabfRt8Mh8DEKciOoA4-xmDsg3MYqUOk791Qh0irMdKp7dWp6w9N9xmmvwH1a--c</recordid><startdate>20131217</startdate><enddate>20131217</enddate><creator>Zhang, Zhaiyi</creator><creator>Convertini, Paolo</creator><creator>Shen, Manli</creator><creator>Xu, Xiu</creator><creator>Lemoine, Frédéric</creator><creator>de la Grange, Pierre</creator><creator>Andres, Douglas A</creator><creator>Stamm, Stefan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131217</creationdate><title>Valproic acid causes proteasomal degradation of DICER and influences miRNA expression</title><author>Zhang, Zhaiyi ; Convertini, Paolo ; Shen, Manli ; Xu, Xiu ; Lemoine, Frédéric ; de la Grange, Pierre ; Andres, Douglas A ; Stamm, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-967a201681ec527251106451bb2ff9223be34a98afe4ad578f69af7d971570b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acids</topic><topic>Apoptosis</topic><topic>Arrays</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Cell death</topic><topic>Cells, Cultured</topic><topic>DEAD-box RNA Helicases - metabolism</topic><topic>Degradation</topic><topic>Dicer protein</topic><topic>Epilepsy</topic><topic>Extracellular signal-regulated kinase</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinases</topic><topic>Microarray Analysis</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Physiology</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Proteasomes</topic><topic>Proteins</topic><topic>Proteolysis - drug effects</topic><topic>Ribonuclease III - metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Rodents</topic><topic>Valproic acid</topic><topic>Valproic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhaiyi</creatorcontrib><creatorcontrib>Convertini, Paolo</creatorcontrib><creatorcontrib>Shen, Manli</creatorcontrib><creatorcontrib>Xu, Xiu</creatorcontrib><creatorcontrib>Lemoine, Frédéric</creatorcontrib><creatorcontrib>de la Grange, Pierre</creatorcontrib><creatorcontrib>Andres, Douglas A</creatorcontrib><creatorcontrib>Stamm, Stefan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24358235</pmid><doi>10.1371/journal.pone.0082895</doi><tpages>e82895</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Apoptosis Arrays Autophagy Biochemistry Bioinformatics Cell death Cells, Cultured DEAD-box RNA Helicases - metabolism Degradation Dicer protein Epilepsy Extracellular signal-regulated kinase Gene expression Gene Expression Profiling Gene Expression Regulation - drug effects Genes Genetic aspects Genomes HEK293 Cells HeLa Cells Humans Kinases Microarray Analysis MicroRNA MicroRNAs - genetics MicroRNAs - metabolism miRNA Physiology Proteasome Endopeptidase Complex - metabolism Proteasomes Proteins Proteolysis - drug effects Ribonuclease III - metabolism Ribonucleic acid RNA Rodents Valproic acid Valproic Acid - pharmacology |
| title | Valproic acid causes proteasomal degradation of DICER and influences miRNA expression |
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