Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures
Background: Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which requir...
Gespeichert in:
| Veröffentlicht in: | Pediatric research 2016-07, Vol.80 (1), p.145-150 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 150 |
|---|---|
| container_issue | 1 |
| container_start_page | 145 |
| container_title | Pediatric research |
| container_volume | 80 |
| creator | White, Kimberly M.R. Sabatino, Julia A. He, Min Davis, Natalie Tang, Ningfeng Bearer, Cynthia F. |
| description | Background:
Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts. Our objective is to determine if toluene inhibits L1-mediated NOG and toluene inhibits L1 signaling at concentrations achieved during occupational exposure.
Methods:
Concentrations of toluene reflective of blood concentrations achieved in solvent abusers and occupational settings are used. Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2 h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2 activation by L1 in CGN is analyzed by immunoblot.
Results:
Toluene significantly reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene significantly reduced L1-mediated ERK1/2 phosphorylation.
Conclusion:
Results suggest that toluene inhibits L1-lipid raft interactions at occupationally relevant concentrations and may lead to a fetal solvent spectrum disorder similar to fetal alcohol spectrum disorder. |
| doi_str_mv | 10.1038/pr.2016.40 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4929035</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4265628161</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-16764b6d11c04f22e68af08de44b9f9e3fce0cff74d1a51bd29d408ade89cc9c3</originalsourceid><addsrcrecordid>eNplkUFP3DAQha0KVBbaS39AZYkLapXt2PEm8aVShUpBWokLnC2vPWaDsnFqx7T8e5wGEJSTNX6fnp_nEfKJwZJB2XwbwpIDq5YC3pEFW5VQgBD1HlkAlKwopWwOyGGMtwBMrBrxnhzwGnhdc7Yg91e-S9gjtW0MaRhb31Pv6LhF6lJvpjlOF2tGDXYd1XaLcYJ2vkOTOqR6pMb3Bvsx6BnXMXrT6hEt_dOOW-qNScM_TXcU_w4-poDxA9l3uov48fE8ItdnP69Oz4v15a-L0x_rwgjBx4JVdSU2lWXMgHCcY9VoB41FITbSSSydQTDO1cIyvWIby6UV0GiLjTRGmvKIfJ99h7TZoZ2DdmoI7U6He-V1q14rfbtVN_5OCckllKtscPJoEPzvhHFUuzZOy9A9-hQVa_JeS-AgM3r8H3rrU8jfnqjcicjFVJn6MlMm-BgDuucwDNTUaJ7V1KgSkOHPL-M_o08VZuDrDMQs9TcYXrz51u4Bo5-uFQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1844740446</pqid></control><display><type>article</type><title>Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>White, Kimberly M.R. ; Sabatino, Julia A. ; He, Min ; Davis, Natalie ; Tang, Ningfeng ; Bearer, Cynthia F.</creator><creatorcontrib>White, Kimberly M.R. ; Sabatino, Julia A. ; He, Min ; Davis, Natalie ; Tang, Ningfeng ; Bearer, Cynthia F.</creatorcontrib><description>Background:
Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts. Our objective is to determine if toluene inhibits L1-mediated NOG and toluene inhibits L1 signaling at concentrations achieved during occupational exposure.
Methods:
Concentrations of toluene reflective of blood concentrations achieved in solvent abusers and occupational settings are used. Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2 h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2 activation by L1 in CGN is analyzed by immunoblot.
Results:
Toluene significantly reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene significantly reduced L1-mediated ERK1/2 phosphorylation.
Conclusion:
Results suggest that toluene inhibits L1-lipid raft interactions at occupationally relevant concentrations and may lead to a fetal solvent spectrum disorder similar to fetal alcohol spectrum disorder.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/pr.2016.40</identifier><identifier>PMID: 27027721</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/136/368 ; 692/699/375/2764/3195 ; Animals ; basic-science-investigation ; Cell adhesion & migration ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Fetal alcohol syndrome ; Laminin - metabolism ; Maternal Exposure ; Medicine & Public Health ; Membrane Microdomains ; Neural Cell Adhesion Molecule L1 - metabolism ; Neurites - drug effects ; Neurobiology ; Neurons ; Neurons - drug effects ; Occupational Exposure - prevention & control ; Pediatric Surgery ; Pediatrics ; Phosphorylation ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Solvent abuse ; Toluene - adverse effects</subject><ispartof>Pediatric research, 2016-07, Vol.80 (1), p.145-150</ispartof><rights>International Pediatric Research Foundation, Inc. 2016</rights><rights>Copyright Nature Publishing Group Jul 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-16764b6d11c04f22e68af08de44b9f9e3fce0cff74d1a51bd29d408ade89cc9c3</citedby><cites>FETCH-LOGICAL-c442t-16764b6d11c04f22e68af08de44b9f9e3fce0cff74d1a51bd29d408ade89cc9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27027721$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>White, Kimberly M.R.</creatorcontrib><creatorcontrib>Sabatino, Julia A.</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Davis, Natalie</creatorcontrib><creatorcontrib>Tang, Ningfeng</creatorcontrib><creatorcontrib>Bearer, Cynthia F.</creatorcontrib><title>Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background:
Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts. Our objective is to determine if toluene inhibits L1-mediated NOG and toluene inhibits L1 signaling at concentrations achieved during occupational exposure.
Methods:
Concentrations of toluene reflective of blood concentrations achieved in solvent abusers and occupational settings are used. Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2 h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2 activation by L1 in CGN is analyzed by immunoblot.
Results:
Toluene significantly reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene significantly reduced L1-mediated ERK1/2 phosphorylation.
Conclusion:
Results suggest that toluene inhibits L1-lipid raft interactions at occupationally relevant concentrations and may lead to a fetal solvent spectrum disorder similar to fetal alcohol spectrum disorder.</description><subject>631/136/368</subject><subject>692/699/375/2764/3195</subject><subject>Animals</subject><subject>basic-science-investigation</subject><subject>Cell adhesion & migration</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Fetal alcohol syndrome</subject><subject>Laminin - metabolism</subject><subject>Maternal Exposure</subject><subject>Medicine & Public Health</subject><subject>Membrane Microdomains</subject><subject>Neural Cell Adhesion Molecule L1 - metabolism</subject><subject>Neurites - drug effects</subject><subject>Neurobiology</subject><subject>Neurons</subject><subject>Neurons - drug effects</subject><subject>Occupational Exposure - prevention & control</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Phosphorylation</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Solvent abuse</subject><subject>Toluene - adverse effects</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNplkUFP3DAQha0KVBbaS39AZYkLapXt2PEm8aVShUpBWokLnC2vPWaDsnFqx7T8e5wGEJSTNX6fnp_nEfKJwZJB2XwbwpIDq5YC3pEFW5VQgBD1HlkAlKwopWwOyGGMtwBMrBrxnhzwGnhdc7Yg91e-S9gjtW0MaRhb31Pv6LhF6lJvpjlOF2tGDXYd1XaLcYJ2vkOTOqR6pMb3Bvsx6BnXMXrT6hEt_dOOW-qNScM_TXcU_w4-poDxA9l3uov48fE8ItdnP69Oz4v15a-L0x_rwgjBx4JVdSU2lWXMgHCcY9VoB41FITbSSSydQTDO1cIyvWIby6UV0GiLjTRGmvKIfJ99h7TZoZ2DdmoI7U6He-V1q14rfbtVN_5OCckllKtscPJoEPzvhHFUuzZOy9A9-hQVa_JeS-AgM3r8H3rrU8jfnqjcicjFVJn6MlMm-BgDuucwDNTUaJ7V1KgSkOHPL-M_o08VZuDrDMQs9TcYXrz51u4Bo5-uFQ</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>White, Kimberly M.R.</creator><creator>Sabatino, Julia A.</creator><creator>He, Min</creator><creator>Davis, Natalie</creator><creator>Tang, Ningfeng</creator><creator>Bearer, Cynthia F.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160701</creationdate><title>Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures</title><author>White, Kimberly M.R. ; Sabatino, Julia A. ; He, Min ; Davis, Natalie ; Tang, Ningfeng ; Bearer, Cynthia F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-16764b6d11c04f22e68af08de44b9f9e3fce0cff74d1a51bd29d408ade89cc9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/136/368</topic><topic>692/699/375/2764/3195</topic><topic>Animals</topic><topic>basic-science-investigation</topic><topic>Cell adhesion & migration</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Fetal alcohol syndrome</topic><topic>Laminin - metabolism</topic><topic>Maternal Exposure</topic><topic>Medicine & Public Health</topic><topic>Membrane Microdomains</topic><topic>Neural Cell Adhesion Molecule L1 - metabolism</topic><topic>Neurites - drug effects</topic><topic>Neurobiology</topic><topic>Neurons</topic><topic>Neurons - drug effects</topic><topic>Occupational Exposure - prevention & control</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Phosphorylation</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Solvent abuse</topic><topic>Toluene - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>White, Kimberly M.R.</creatorcontrib><creatorcontrib>Sabatino, Julia A.</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Davis, Natalie</creatorcontrib><creatorcontrib>Tang, Ningfeng</creatorcontrib><creatorcontrib>Bearer, Cynthia F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>White, Kimberly M.R.</au><au>Sabatino, Julia A.</au><au>He, Min</au><au>Davis, Natalie</au><au>Tang, Ningfeng</au><au>Bearer, Cynthia F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>80</volume><issue>1</issue><spage>145</spage><epage>150</epage><pages>145-150</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background:
Prenatal toluene exposure can cause neurodevelopmental disabilities similar to fetal alcohol syndrome. Both share neuroanatomic pathologies similar to children with mutations in L1 cell adhesion molecule (L1). L1 mediates neurite outgrowth (NOG) via signaling through ERK1/2, which require trafficking of L1 through lipid rafts. Our objective is to determine if toluene inhibits L1-mediated NOG and toluene inhibits L1 signaling at concentrations achieved during occupational exposure.
Methods:
Concentrations of toluene reflective of blood concentrations achieved in solvent abusers and occupational settings are used. Cerebellar granule neurons (CGN) harvested from postnatal day 6 rat pups are plated on coverslips coated with poly-L-lysine (PLL) alone or PLL followed by laminin. L1 is added to the media of CGN plated on PLL alone. Toluene is added 2 h after plating. Cells are fixed at 24 h and neurite length is measured. ERK1/2 activation by L1 in CGN is analyzed by immunoblot.
Results:
Toluene significantly reduced mean neurite length of CGN exposed to L1 but not laminin. Toluene significantly reduced L1-mediated ERK1/2 phosphorylation.
Conclusion:
Results suggest that toluene inhibits L1-lipid raft interactions at occupationally relevant concentrations and may lead to a fetal solvent spectrum disorder similar to fetal alcohol spectrum disorder.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>27027721</pmid><doi>10.1038/pr.2016.40</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-3998 |
| ispartof | Pediatric research, 2016-07, Vol.80 (1), p.145-150 |
| issn | 0031-3998 1530-0447 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4929035 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 631/136/368 692/699/375/2764/3195 Animals basic-science-investigation Cell adhesion & migration Extracellular Signal-Regulated MAP Kinases - metabolism Female Fetal alcohol syndrome Laminin - metabolism Maternal Exposure Medicine & Public Health Membrane Microdomains Neural Cell Adhesion Molecule L1 - metabolism Neurites - drug effects Neurobiology Neurons Neurons - drug effects Occupational Exposure - prevention & control Pediatric Surgery Pediatrics Phosphorylation Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Sprague-Dawley Solvent abuse Toluene - adverse effects |
| title | Toluene disruption of the functions of L1 cell adhesion molecule at concentrations associated with occupational exposures |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T19%3A16%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Toluene%20disruption%20of%20the%20functions%20of%20L1%20cell%20adhesion%20molecule%20at%20concentrations%20associated%20with%20occupational%20exposures&rft.jtitle=Pediatric%20research&rft.au=White,%20Kimberly%20M.R.&rft.date=2016-07-01&rft.volume=80&rft.issue=1&rft.spage=145&rft.epage=150&rft.pages=145-150&rft.issn=0031-3998&rft.eissn=1530-0447&rft_id=info:doi/10.1038/pr.2016.40&rft_dat=%3Cproquest_pubme%3E4265628161%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1844740446&rft_id=info:pmid/27027721&rfr_iscdi=true |