p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging
Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. Wild type and p38α...
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| Veröffentlicht in: | PloS one 2017-02, Vol.12 (2), p.e0171738-e0171738 |
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| creator | Tormos, Ana M Rius-Pérez, Sergio Jorques, María Rada, Patricia Ramirez, Lorena Valverde, Ángela M Nebreda, Ángel R Sastre, Juan Taléns-Visconti, Raquel |
| description | Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging.
Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used.
We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization and a dramatic loss of actin cytoskeleton. This was associated with abnormal hyperactivation of RhoA and Cdc42 GTPases. Long-term p38α deficiency drives to inactivation of HSP27, which seems to account for the impairment in actin cytoskeleton as Hsp27-silencing decreased the number and length of actin filaments in isolated hepatocytes.
p38α MAPK is essential for actin dynamics with age in hepatocytes. |
| doi_str_mv | 10.1371/journal.pone.0171738 |
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Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used.
We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization and a dramatic loss of actin cytoskeleton. This was associated with abnormal hyperactivation of RhoA and Cdc42 GTPases. Long-term p38α deficiency drives to inactivation of HSP27, which seems to account for the impairment in actin cytoskeleton as Hsp27-silencing decreased the number and length of actin filaments in isolated hepatocytes.
p38α MAPK is essential for actin dynamics with age in hepatocytes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0171738</identifier><identifier>PMID: 28166285</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Actins - chemistry ; Actins - metabolism ; Adults ; Aging ; Animals ; Biology and Life Sciences ; Biomarkers ; Cdc42 protein ; Cell cycle ; Cell division ; Cells, Cultured ; Cellular Senescence ; Cyclin B1 ; Cyclin D1 ; Cytokinesis ; Cytokinesis - genetics ; Cytoskeleton ; Cytoskeleton - metabolism ; Deactivation ; Diabetes ; Dismantling ; Failure ; Filaments ; Gene expression ; Gene Knockout Techniques ; Heat shock proteins ; Hepatocytes ; Hepatocytes - physiology ; Hsp27 protein ; Immunohistochemistry ; Inactivation ; Inflammatory diseases ; Kinases ; Liver ; Liver cancer ; Male ; MAP kinase ; Medicine and Health Sciences ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 14 - genetics ; Mitogen-Activated Protein Kinase 14 - metabolism ; Mitosis - genetics ; Phosphorylation ; Physiology ; Polymerization ; Polyploidy ; Protein Binding ; Protein Multimerization ; Protein-Serine-Threonine Kinases - metabolism ; RhoA protein ; Rodents ; S phase ; Weaning</subject><ispartof>PloS one, 2017-02, Vol.12 (2), p.e0171738-e0171738</ispartof><rights>2017 Tormos 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>2017 Tormos et al 2017 Tormos et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-b32e808df29d3e8001592afe85c23d339787d6257f1d7b1636a1cbe2e4101c743</citedby><cites>FETCH-LOGICAL-c526t-b32e808df29d3e8001592afe85c23d339787d6257f1d7b1636a1cbe2e4101c743</cites><orcidid>0000-0002-9816-9693</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293263/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293263/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28166285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Avila, Matias A</contributor><creatorcontrib>Tormos, Ana M</creatorcontrib><creatorcontrib>Rius-Pérez, Sergio</creatorcontrib><creatorcontrib>Jorques, María</creatorcontrib><creatorcontrib>Rada, Patricia</creatorcontrib><creatorcontrib>Ramirez, Lorena</creatorcontrib><creatorcontrib>Valverde, Ángela M</creatorcontrib><creatorcontrib>Nebreda, Ángel R</creatorcontrib><creatorcontrib>Sastre, Juan</creatorcontrib><creatorcontrib>Taléns-Visconti, Raquel</creatorcontrib><title>p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging.
Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used.
We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization and a dramatic loss of actin cytoskeleton. This was associated with abnormal hyperactivation of RhoA and Cdc42 GTPases. Long-term p38α deficiency drives to inactivation of HSP27, which seems to account for the impairment in actin cytoskeleton as Hsp27-silencing decreased the number and length of actin filaments in isolated hepatocytes.
p38α MAPK is essential for actin dynamics with age in hepatocytes.</description><subject>Actin</subject><subject>Actins - chemistry</subject><subject>Actins - metabolism</subject><subject>Adults</subject><subject>Aging</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Cdc42 protein</subject><subject>Cell cycle</subject><subject>Cell division</subject><subject>Cells, Cultured</subject><subject>Cellular Senescence</subject><subject>Cyclin B1</subject><subject>Cyclin D1</subject><subject>Cytokinesis</subject><subject>Cytokinesis - genetics</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - metabolism</subject><subject>Deactivation</subject><subject>Diabetes</subject><subject>Dismantling</subject><subject>Failure</subject><subject>Filaments</subject><subject>Gene expression</subject><subject>Gene Knockout Techniques</subject><subject>Heat shock proteins</subject><subject>Hepatocytes</subject><subject>Hepatocytes - physiology</subject><subject>Hsp27 protein</subject><subject>Immunohistochemistry</subject><subject>Inactivation</subject><subject>Inflammatory diseases</subject><subject>Kinases</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitogen-Activated Protein Kinase 14 - genetics</subject><subject>Mitogen-Activated Protein Kinase 14 - metabolism</subject><subject>Mitosis - genetics</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Polymerization</subject><subject>Polyploidy</subject><subject>Protein Binding</subject><subject>Protein Multimerization</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>RhoA protein</subject><subject>Rodents</subject><subject>S phase</subject><subject>Weaning</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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>eNptUstuFDEQHCEQCYE_QDASFy67uO3xYy5IUcQjUiQucMXy2O3NbLzjwZ6JlM_iR_gmnN1JlCBOtqqrqrvtqqrXQNbAJHzYxjkNJqzHOOCagATJ1JPqGFpGV4IS9vTB_ah6kfOWEM6UEM-rI6pACKr4cfVzZOrP7zrhZg5mwlwbO_VDbW-mmK8w4BSH2gxuD1z1A-Y-16V-iaOZYgGLws2pHza1w2sMcdzhMO0VZlPQl9Uzb0LGV8t5Uv34_On72dfVxbcv52enFyvLqZhWHaOoiHKeto6VGwHeUuNRcUuZY6yVSjpBufTgZAeCCQO2Q4oNELCyYSfV24PvGGLWy9NkDUrwpm1aRQvj_MBw0Wz1mPqdSTc6ml7vgZg22qSptwG1YYKB9055IhsiXcuc9x1I60Ci57x4fVy6zd0OnS0rJxMemT6uDP2l3sRrzWn5EcGKwfvFIMVfM-ZJ7_psMQQzYJwPcysKsO_17h_q_7drDiybYs4J_f0wQPRtXO5U-jYueolLkb15uMi96C4f7C_J28AE</recordid><startdate>20170206</startdate><enddate>20170206</enddate><creator>Tormos, Ana M</creator><creator>Rius-Pérez, Sergio</creator><creator>Jorques, María</creator><creator>Rada, Patricia</creator><creator>Ramirez, Lorena</creator><creator>Valverde, Ángela M</creator><creator>Nebreda, Ángel R</creator><creator>Sastre, Juan</creator><creator>Taléns-Visconti, Raquel</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>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>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9816-9693</orcidid></search><sort><creationdate>20170206</creationdate><title>p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging</title><author>Tormos, Ana M ; Rius-Pérez, Sergio ; Jorques, María ; Rada, Patricia ; Ramirez, Lorena ; Valverde, Ángela M ; Nebreda, Ángel R ; Sastre, Juan ; Taléns-Visconti, Raquel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-b32e808df29d3e8001592afe85c23d339787d6257f1d7b1636a1cbe2e4101c743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Actin</topic><topic>Actins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tormos, Ana M</au><au>Rius-Pérez, Sergio</au><au>Jorques, María</au><au>Rada, Patricia</au><au>Ramirez, Lorena</au><au>Valverde, Ángela M</au><au>Nebreda, Ángel R</au><au>Sastre, Juan</au><au>Taléns-Visconti, Raquel</au><au>Avila, Matias A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-02-06</date><risdate>2017</risdate><volume>12</volume><issue>2</issue><spage>e0171738</spage><epage>e0171738</epage><pages>e0171738-e0171738</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging.
Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used.
We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization and a dramatic loss of actin cytoskeleton. This was associated with abnormal hyperactivation of RhoA and Cdc42 GTPases. Long-term p38α deficiency drives to inactivation of HSP27, which seems to account for the impairment in actin cytoskeleton as Hsp27-silencing decreased the number and length of actin filaments in isolated hepatocytes.
p38α MAPK is essential for actin dynamics with age in hepatocytes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28166285</pmid><doi>10.1371/journal.pone.0171738</doi><orcidid>https://orcid.org/0000-0002-9816-9693</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| source | PLoS; MEDLINE; PubMed Central; Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Actin Actins - chemistry Actins - metabolism Adults Aging Animals Biology and Life Sciences Biomarkers Cdc42 protein Cell cycle Cell division Cells, Cultured Cellular Senescence Cyclin B1 Cyclin D1 Cytokinesis Cytokinesis - genetics Cytoskeleton Cytoskeleton - metabolism Deactivation Diabetes Dismantling Failure Filaments Gene expression Gene Knockout Techniques Heat shock proteins Hepatocytes Hepatocytes - physiology Hsp27 protein Immunohistochemistry Inactivation Inflammatory diseases Kinases Liver Liver cancer Male MAP kinase Medicine and Health Sciences Mice Mice, Knockout Mitogen-Activated Protein Kinase 14 - genetics Mitogen-Activated Protein Kinase 14 - metabolism Mitosis - genetics Phosphorylation Physiology Polymerization Polyploidy Protein Binding Protein Multimerization Protein-Serine-Threonine Kinases - metabolism RhoA protein Rodents S phase Weaning |
| title | p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T18%3A44%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=p38%CE%B1%20regulates%20actin%20cytoskeleton%20and%20cytokinesis%20in%20hepatocytes%20during%20development%20and%20aging&rft.jtitle=PloS%20one&rft.au=Tormos,%20Ana%20M&rft.date=2017-02-06&rft.volume=12&rft.issue=2&rft.spage=e0171738&rft.epage=e0171738&rft.pages=e0171738-e0171738&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0171738&rft_dat=%3Cproquest_plos_%3E1865821155%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1865494982&rft_id=info:pmid/28166285&rft_doaj_id=oai_doaj_org_article_a3631ffd8f07407d93dffb17cd17ef55&rfr_iscdi=true |