Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.
Identifieur interne : 000B67 ( Main/Exploration ); précédent : 000B66; suivant : 000B68Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.
Auteurs : Jutta Bonifas [Allemagne] ; 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
Affiliations:
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Le document en format XML
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<term>Cell Survival (drug effects)</term>
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<term>Phenylenediamines (adverse effects)</term>
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<term>Reverse Transcriptase Polymerase Chain Reaction</term>
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<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>
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