Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes
Identifieur interne : 001B99 ( Istex/Corpus ); précédent : 001B98; suivant : 001C00Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes
Auteurs : Michaela Kalmes ; Jenny Hennen ; Judith Clemens ; Brunhilde BlömekeSource :
- Biological Chemistry [ 1431-6730 ] ; 2011-07-01.
Abstract
While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.
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DOI: 10.1515/bc.2011.067
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title><author><name sortKey="Kalmes, Michaela" sort="Kalmes, Michaela" uniqKey="Kalmes M" first="Michaela" last="Kalmes">Michaela Kalmes</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hennen, Jenny" sort="Hennen, Jenny" uniqKey="Hennen J" first="Jenny" last="Hennen">Jenny Hennen</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Clemens, Judith" sort="Clemens, Judith" uniqKey="Clemens J" first="Judith" last="Clemens">Judith Clemens</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Blomeke, Brunhilde" sort="Blomeke, Brunhilde" uniqKey="Blomeke B" first="Brunhilde" last="Blömeke">Brunhilde Blömeke</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:93D8B9C52830D45D5811C96358F11DD2DBC4DAB6</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1515/bc.2011.067</idno><idno type="url">https://api.istex.fr/document/93D8B9C52830D45D5811C96358F11DD2DBC4DAB6/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001B99</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001B99</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title><author><name sortKey="Kalmes, Michaela" sort="Kalmes, Michaela" uniqKey="Kalmes M" first="Michaela" last="Kalmes">Michaela Kalmes</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hennen, Jenny" sort="Hennen, Jenny" uniqKey="Hennen J" first="Jenny" last="Hennen">Jenny Hennen</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Clemens, Judith" sort="Clemens, Judith" uniqKey="Clemens J" first="Judith" last="Clemens">Judith Clemens</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Blomeke, Brunhilde" sort="Blomeke, Brunhilde" uniqKey="Blomeke B" first="Brunhilde" last="Blömeke">Brunhilde Blömeke</name><affiliation><mods:affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Biological Chemistry</title><title level="j" type="abbrev">Biological Chemistry</title><idno type="ISSN">1431-6730</idno><idno type="eISSN">1437-4315</idno><imprint><publisher>Walter de Gruyter</publisher><date type="published" when="2011-07-01">2011-07-01</date><biblScope unit="volume">392</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="643">643</biblScope><biblScope unit="page" to="651">651</biblScope></imprint><idno type="ISSN">1431-6730</idno></series><idno type="istex">93D8B9C52830D45D5811C96358F11DD2DBC4DAB6</idno><idno type="DOI">10.1515/bc.2011.067</idno><idno type="ArticleID">bc.2011.067</idno><idno type="pdf">bc.2011.067.pdf</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1431-6730</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.</div></front></TEI><istex><corpusName>degruyter-journals</corpusName><author><json:item><name>Michaela Kalmes</name><affiliations><json:string>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</json:string></affiliations></json:item><json:item><name>Jenny Hennen</name><affiliations><json:string>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</json:string></affiliations></json:item><json:item><name>Judith Clemens</name><affiliations><json:string>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</json:string></affiliations></json:item><json:item><name>Brunhilde Blömeke</name><affiliations><json:string>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>cytochrome P450 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>interleukin-8</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>physiological AhR function</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>proliferation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>skin cells</value></json:item></subject><articleId><json:string>bc.2011.067</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.</abstract><qualityIndicators><score>9.46</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.245 x 793.66 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1347</abstractCharCount><pdfWordCount>6296</pdfWordCount><pdfCharCount>39398</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>205</abstractWordCount></qualityIndicators><title>Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title><refBibs><json:item><author><json:item><name>M Abdelrahim</name></json:item><json:item><name>R Smith</name></json:item><json:item><name>S Safe</name></json:item></author><host><volume>63</volume><pages><last>1381</last><first>1373</first></pages><author></author><title>Mol. 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Cancer</title><publicationDate>1970</publicationDate></host><title>Inter- leukin-8/CXCL8 is a growth factor for human lung cancer cells</title><publicationDate>1970</publicationDate></json:item></refBibs><genre><json:string>research-article</json:string></genre><host><volume>392</volume><publisherId><json:string>bchm</json:string></publisherId><pages><last>651</last><first>643</first></pages><issn><json:string>1431-6730</json:string></issn><issue>7</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1437-4315</json:string></eissn><title>Biological Chemistry</title></host><categories><wos><json:string>science</json:string><json:string>biochemistry & molecular biology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>biomedical research</json:string><json:string>biochemistry & molecular biology</json:string></scienceMetrix></categories><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1515/bc.2011.067</json:string></doi><id>93D8B9C52830D45D5811C96358F11DD2DBC4DAB6</id><score>1.3813844</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/93D8B9C52830D45D5811C96358F11DD2DBC4DAB6/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/93D8B9C52830D45D5811C96358F11DD2DBC4DAB6/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/93D8B9C52830D45D5811C96358F11DD2DBC4DAB6/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Walter de Gruyter</publisher><availability><p>©2011 by Walter de Gruyter Berlin Boston, 2011</p></availability><date>2011-06-18</date></publicationStmt><notesStmt><note>Corresponding author</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title><author xml:id="author-1"><persName><forename type="first">Michaela</forename><surname>Kalmes</surname></persName><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation></author><author xml:id="author-2"><persName><forename type="first">Jenny</forename><surname>Hennen</surname></persName><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Judith</forename><surname>Clemens</surname></persName><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Brunhilde</forename><surname>Blömeke</surname></persName><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation></author></analytic><monogr><title level="j">Biological Chemistry</title><title level="j" type="abbrev">Biological Chemistry</title><idno type="pISSN">1431-6730</idno><idno type="eISSN">1437-4315</idno><imprint><publisher>Walter de Gruyter</publisher><date type="published" when="2011-07-01"></date><biblScope unit="volume">392</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="643">643</biblScope><biblScope unit="page" to="651">651</biblScope></imprint></monogr><idno type="istex">93D8B9C52830D45D5811C96358F11DD2DBC4DAB6</idno><idno type="DOI">10.1515/bc.2011.067</idno><idno type="ArticleID">bc.2011.067</idno><idno type="pdf">bc.2011.067.pdf</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011-06-18</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>cytochrome P450 1</term></item><item><term>interleukin-8</term></item><item><term>physiological AhR function</term></item><item><term>proliferation</term></item><item><term>skin cells</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-06-18">Created</change><change when="2011-07-01">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2017-01-17">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/93D8B9C52830D45D5811C96358F11DD2DBC4DAB6/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus degruyter-journals" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//Atypon//DTD Atypon Systems Archival NLM DTD Suite v2.2.0 20090301//EN" URI="nlm-dtd/archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article" xml:lang="EN"><front><journal-meta><journal-id journal-id-type="publisher-id">bchm</journal-id><abbrev-journal-title abbrev-type="full">Biological Chemistry</abbrev-journal-title><issn pub-type="epub">1437-4315</issn><issn pub-type="ppub">1431-6730</issn><publisher><publisher-name>Walter de Gruyter</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">bc.2011.067</article-id><article-id pub-id-type="doi">10.1515/bc.2011.067</article-id><article-categories><subj-group subj-group-type="heading"><subject>CELL BIOLOGY AND SIGNALING</subject></subj-group></article-categories><title-group><article-title>Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</article-title></title-group><contrib-group><contrib contrib-type="author"><name name-style="western"><given-names>Michaela</given-names><x> </x><surname>Kalmes</surname></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><x>, </x></contrib><contrib contrib-type="author"><name name-style="western"><given-names>Jenny</given-names><x> </x><surname>Hennen</surname></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><x>, </x></contrib><contrib contrib-type="author"><name name-style="western"><given-names>Judith</given-names><x> </x><surname>Clemens</surname></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><x>, </x></contrib><contrib contrib-type="author"><name name-style="western"><given-names>Brunhilde</given-names><x> </x><surname>Blömeke</surname></name><email>bloemeke@uni-trier.de</email><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><x>, </x></contrib><aff id="aff1"><sup>1</sup>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</aff></contrib-group><author-notes><corresp>Corresponding author</corresp></author-notes><pub-date pub-type="ppub"><day>01</day><month>07</month><year>2011</year><string-date>July 2011</string-date></pub-date><pub-date pub-type="epub"><day>18</day><month>06</month><year>2011</year></pub-date><volume>392</volume><issue>7</issue><fpage>643</fpage><lpage>651</lpage><history><date date-type="received"><day>9</day><month>9</month><year>2010</year></date><date date-type="accepted"><day>18</day><month>4</month><year>2011</year></date></history><copyright-statement>©2011 by Walter de Gruyter Berlin Boston</copyright-statement><copyright-year>2011</copyright-year><related-article related-article-type="pdf" xlink:href="bc.2011.067.pdf"></related-article><abstract><title>Abstract</title><p>While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27<sup>KIP1</sup> was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.</p></abstract><kwd-group><title>Keywords</title><kwd>cytochrome P450 1</kwd><x>, </x><kwd>interleukin-8</kwd><x>, </x><kwd>physiological AhR function</kwd><x>, </x><kwd>proliferation</kwd><x>, </x><kwd>skin cells</kwd></kwd-group><counts><fig-count count="5"></fig-count><table-count count="0"></table-count><ref-count count="49"></ref-count></counts></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes</title></titleInfo><name type="personal"><namePart type="given">Michaela</namePart><namePart type="family">Kalmes</namePart><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jenny</namePart><namePart type="family">Hennen</namePart><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Judith</namePart><namePart type="family">Clemens</namePart><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Brunhilde</namePart><namePart type="family">Blömeke</namePart><affiliation>Department of Environmental Toxicology, University of Trier, Universitätsring 15, D-54296 Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Walter de Gruyter</publisher><dateIssued encoding="w3cdtf">2011-07-01</dateIssued><dateCreated encoding="w3cdtf">2011-06-18</dateCreated><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">5</extent><extent unit="references">49</extent></physicalDescription><abstract lang="en">While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.</abstract><note type="author-notes">Corresponding author</note><subject><genre>Keywords</genre><topic>cytochrome P450 1</topic><topic>interleukin-8</topic><topic>physiological AhR function</topic><topic>proliferation</topic><topic>skin cells</topic></subject><relatedItem type="host"><titleInfo><title>Biological Chemistry</title></titleInfo><titleInfo type="abbreviated"><title>Biological Chemistry</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">1431-6730</identifier><identifier type="eISSN">1437-4315</identifier><identifier type="PublisherID">bchm</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>392</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>643</start><end>651</end></extent></part></relatedItem><identifier type="istex">93D8B9C52830D45D5811C96358F11DD2DBC4DAB6</identifier><identifier type="DOI">10.1515/bc.2011.067</identifier><identifier type="ArticleID">bc.2011.067</identifier><identifier type="pdf">bc.2011.067.pdf</identifier><accessCondition type="use and reproduction" contentType="copyright">©2011 by Walter de Gruyter Berlin Boston, 2011</accessCondition><recordInfo><recordContentSource>De Gruyter</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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