Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.
Identifieur interne : 000532 ( PubMed/Corpus ); précédent : 000531; suivant : 000533Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.
Auteurs : Jutta Bonifas ; Simone Scheitza ; Judith Clemens ; Brunhilde BlömekeSource :
- The Journal of pharmacology and experimental therapeutics [ 1521-0103 ] ; 2010.
English descriptors
- KwdEn :
- Acetylation, Arylamine N-Acetyltransferase (antagonists & inhibitors), Arylamine N-Acetyltransferase (biosynthesis), Cell Culture Techniques, Cell Cycle (drug effects), Cell Line, Cell Proliferation (drug effects), Cell Survival (drug effects), Dose-Response Relationship, Drug, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Hair Dyes (adverse effects), Hair Dyes (chemistry), Humans, Isoenzymes (antagonists & inhibitors), Isoenzymes (biosynthesis), Keratinocytes (cytology), Keratinocytes (drug effects), Keratinocytes (enzymology), Phenylenediamines (adverse effects), Phenylenediamines (chemistry), Reverse Transcriptase Polymerase Chain Reaction, Substrate Specificity, Time Factors.
- MESH :
- chemical , adverse effects : Hair Dyes, Phenylenediamines.
- chemical , antagonists & inhibitors : Arylamine N-Acetyltransferase, Isoenzymes.
- chemical , biosynthesis : Arylamine N-Acetyltransferase, Isoenzymes.
- chemical , chemistry : Hair Dyes, Phenylenediamines.
- cytology : Keratinocytes.
- drug effects : Cell Cycle, Cell Proliferation, Cell Survival, Keratinocytes.
- enzymology : Keratinocytes.
- Acetylation, Cell Culture Techniques, Cell Line, Dose-Response Relationship, Drug, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Humans, Reverse Transcriptase Polymerase Chain Reaction, Substrate Specificity, Time Factors.
Abstract
N-acetyltransferase 1 (NAT1)-mediated N-acetylation in keratinocytes is an important detoxification pathway for the hair dye ingredient para-phenylenediamine (PPD). Because NAT1 can be regulated by various exogenous compounds, including some NAT1 substrates themselves, we investigated NAT1 expression in keratinocytes and the interactions between PPD and NAT1. NAT1 activity was found to be cell-cycle phase-dependent. Maximum NAT1 activities (mean: 49.7 nmol/mg/min) were estimated when HaCaT keratinocytes were arrested in G(0)/G(1) phase, whereas nonsynchronized cells showed the lowest activities (mean: 28.9 nmol/mg/min). It is noteworthy that we also found an accelerated progression through the cell cycle in HaCaT cells with high NAT1 activities. This evidence suggests an association between NAT1 and proliferation in keratinocytes. Regarding the interaction between NAT1 and PPD, we found that keratinocytes N-acetylate PPD; however, this N-acetylation was saturated with increasing PPD concentrations. HaCaT cultured in medium supplemented with PPD (10-200 microM) for 24 h showed a significant concentration-dependent decrease (17-50%) in NAT1 activity. PPD also induced down-regulation of NAT1 activity in human primary keratinocytes. Western blot studies using a NAT1-specific antibody in HaCaT showed that the loss of enzyme activity was associated with a decline in the amount of NAT1 protein, whereas no changes in the amounts of NAT1 P1 (NATb)-dependent mRNA were found by quantitative reverse transcription-polymerase chain reaction analysis, suggesting the involvement of a substrate-dependent mechanism of NAT1 down-regulation. In conclusion, these data show that overall N-acetylation capacity of keratinocytes and consequently detoxification capacities of human skin is modulated by the presence of NAT1 substrates and endogenously by the cell proliferation status of keratinocytes.
DOI: 10.1124/jpet.110.167874
PubMed: 20406859
Links to Exploration step
pubmed:20406859Le document en format XML
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when="2010">2010</date><idno type="RBID">pubmed:20406859</idno><idno type="pmid">20406859</idno><idno type="doi">10.1124/jpet.110.167874</idno><idno type="wicri:Area/PubMed/Corpus">000532</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000532</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.</title><author><name sortKey="Bonifas, Jutta" sort="Bonifas, Jutta" uniqKey="Bonifas J" first="Jutta" last="Bonifas">Jutta Bonifas</name><affiliation><nlm:affiliation>Department of Environmental Toxicology, University Trier, Trier, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Scheitza, Simone" sort="Scheitza, Simone" uniqKey="Scheitza S" first="Simone" last="Scheitza">Simone Scheitza</name></author><author><name sortKey="Clemens, Judith" sort="Clemens, Judith" uniqKey="Clemens J" first="Judith" last="Clemens">Judith Clemens</name></author><author><name sortKey="Blomeke, Brunhilde" sort="Blomeke, Brunhilde" uniqKey="Blomeke B" first="Brunhilde" last="Blömeke">Brunhilde Blömeke</name></author></analytic><series><title level="j">The Journal of pharmacology and experimental therapeutics</title><idno type="eISSN">1521-0103</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetylation</term><term>Arylamine N-Acetyltransferase (antagonists & inhibitors)</term><term>Arylamine N-Acetyltransferase (biosynthesis)</term><term>Cell Culture Techniques</term><term>Cell Cycle (drug effects)</term><term>Cell Line</term><term>Cell Proliferation (drug effects)</term><term>Cell Survival (drug effects)</term><term>Dose-Response Relationship, Drug</term><term>Down-Regulation</term><term>Electrophoresis, Polyacrylamide Gel</term><term>Hair Dyes (adverse effects)</term><term>Hair Dyes (chemistry)</term><term>Humans</term><term>Isoenzymes (antagonists & inhibitors)</term><term>Isoenzymes (biosynthesis)</term><term>Keratinocytes (cytology)</term><term>Keratinocytes (drug effects)</term><term>Keratinocytes (enzymology)</term><term>Phenylenediamines (adverse effects)</term><term>Phenylenediamines (chemistry)</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Substrate Specificity</term><term>Time Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Hair Dyes</term><term>Phenylenediamines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Arylamine N-Acetyltransferase</term><term>Isoenzymes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Arylamine N-Acetyltransferase</term><term>Isoenzymes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Hair Dyes</term><term>Phenylenediamines</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Keratinocytes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Cycle</term><term>Cell Proliferation</term><term>Cell Survival</term><term>Keratinocytes</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Keratinocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Acetylation</term><term>Cell Culture Techniques</term><term>Cell Line</term><term>Dose-Response Relationship, Drug</term><term>Down-Regulation</term><term>Electrophoresis, Polyacrylamide Gel</term><term>Humans</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Substrate Specificity</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">N-acetyltransferase 1 (NAT1)-mediated N-acetylation in keratinocytes is an important detoxification pathway for the hair dye ingredient para-phenylenediamine (PPD). Because NAT1 can be regulated by various exogenous compounds, including some NAT1 substrates themselves, we investigated NAT1 expression in keratinocytes and the interactions between PPD and NAT1. NAT1 activity was found to be cell-cycle phase-dependent. Maximum NAT1 activities (mean: 49.7 nmol/mg/min) were estimated when HaCaT keratinocytes were arrested in G(0)/G(1) phase, whereas nonsynchronized cells showed the lowest activities (mean: 28.9 nmol/mg/min). It is noteworthy that we also found an accelerated progression through the cell cycle in HaCaT cells with high NAT1 activities. This evidence suggests an association between NAT1 and proliferation in keratinocytes. Regarding the interaction between NAT1 and PPD, we found that keratinocytes N-acetylate PPD; however, this N-acetylation was saturated with increasing PPD concentrations. HaCaT cultured in medium supplemented with PPD (10-200 microM) for 24 h showed a significant concentration-dependent decrease (17-50%) in NAT1 activity. PPD also induced down-regulation of NAT1 activity in human primary keratinocytes. Western blot studies using a NAT1-specific antibody in HaCaT showed that the loss of enzyme activity was associated with a decline in the amount of NAT1 protein, whereas no changes in the amounts of NAT1 P1 (NATb)-dependent mRNA were found by quantitative reverse transcription-polymerase chain reaction analysis, suggesting the involvement of a substrate-dependent mechanism of NAT1 down-regulation. In conclusion, these data show that overall N-acetylation capacity of keratinocytes and consequently detoxification capacities of human skin is modulated by the presence of NAT1 substrates and endogenously by the cell proliferation status of keratinocytes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20406859</PMID><DateCreated><Year>2010</Year><Month>06</Month><Day>18</Day></DateCreated><DateCompleted><Year>2010</Year><Month>07</Month><Day>13</Day></DateCompleted><DateRevised><Year>2012</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-0103</ISSN><JournalIssue CitedMedium="Internet"><Volume>334</Volume><Issue>1</Issue><PubDate><Year>2010</Year><Month>Jul</Month></PubDate></JournalIssue><Title>The Journal of pharmacology and experimental therapeutics</Title><ISOAbbreviation>J. Pharmacol. Exp. Ther.</ISOAbbreviation></Journal><ArticleTitle>Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.</ArticleTitle><Pagination><MedlinePgn>318-26</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1124/jpet.110.167874</ELocationID><Abstract><AbstractText>N-acetyltransferase 1 (NAT1)-mediated N-acetylation in keratinocytes is an important detoxification pathway for the hair dye ingredient para-phenylenediamine (PPD). Because NAT1 can be regulated by various exogenous compounds, including some NAT1 substrates themselves, we investigated NAT1 expression in keratinocytes and the interactions between PPD and NAT1. NAT1 activity was found to be cell-cycle phase-dependent. Maximum NAT1 activities (mean: 49.7 nmol/mg/min) were estimated when HaCaT keratinocytes were arrested in G(0)/G(1) phase, whereas nonsynchronized cells showed the lowest activities (mean: 28.9 nmol/mg/min). It is noteworthy that we also found an accelerated progression through the cell cycle in HaCaT cells with high NAT1 activities. This evidence suggests an association between NAT1 and proliferation in keratinocytes. Regarding the interaction between NAT1 and PPD, we found that keratinocytes N-acetylate PPD; however, this N-acetylation was saturated with increasing PPD concentrations. HaCaT cultured in medium supplemented with PPD (10-200 microM) for 24 h showed a significant concentration-dependent decrease (17-50%) in NAT1 activity. PPD also induced down-regulation of NAT1 activity in human primary keratinocytes. Western blot studies using a NAT1-specific antibody in HaCaT showed that the loss of enzyme activity was associated with a decline in the amount of NAT1 protein, whereas no changes in the amounts of NAT1 P1 (NATb)-dependent mRNA were found by quantitative reverse transcription-polymerase chain reaction analysis, suggesting the involvement of a substrate-dependent mechanism of NAT1 down-regulation. In conclusion, these data show that overall N-acetylation capacity of keratinocytes and consequently detoxification capacities of human skin is modulated by the presence of NAT1 substrates and endogenously by the cell proliferation status of keratinocytes.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bonifas</LastName><ForeName>Jutta</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Environmental Toxicology, University Trier, Trier, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scheitza</LastName><ForeName>Simone</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Clemens</LastName><ForeName>Judith</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Blömeke</LastName><ForeName>Brunhilde</ForeName><Initials>B</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>04</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Pharmacol Exp Ther</MedlineTA><NlmUniqueID>0376362</NlmUniqueID><ISSNLinking>0022-3565</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006202">Hair Dyes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007527">Isoenzymes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010655">Phenylenediamines</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.5</RegistryNumber><NameOfSubstance UI="D001191">Arylamine N-Acetyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.3.1.5</RegistryNumber><NameOfSubstance UI="C089384">N-acetyltransferase 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>U770QIT64J</RegistryNumber><NameOfSubstance UI="C029728">4-phenylenediamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000107" MajorTopicYN="N">Acetylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001191" MajorTopicYN="N">Arylamine N-Acetyltransferase</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018929" MajorTopicYN="N">Cell Culture Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002453" MajorTopicYN="N">Cell Cycle</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015536" MajorTopicYN="N">Down-Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004591" MajorTopicYN="N">Electrophoresis, Polyacrylamide Gel</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006202" MajorTopicYN="N">Hair Dyes</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007527" MajorTopicYN="N">Isoenzymes</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015603" MajorTopicYN="N">Keratinocytes</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010655" MajorTopicYN="N">Phenylenediamines</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000737" 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