Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes
Identifieur interne : 000979 ( Main/Exploration ); précédent : 000978; suivant : 000980Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes
Auteurs : Michaela Kalmes [Allemagne] ; Jenny Hennen [Allemagne] ; Judith Clemens [Allemagne] ; Brunhilde Blömeke [Allemagne]Source :
- 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
Affiliations:
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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><affiliations><list><country><li>Allemagne</li></country><region><li>Rhénanie-Palatinat</li></region><settlement><li>Trèves (Allemagne)</li></settlement><orgName><li>Université de Trèves</li></orgName></list><tree><country name="Allemagne"><region name="Rhénanie-Palatinat"><name sortKey="Kalmes, Michaela" sort="Kalmes, Michaela" uniqKey="Kalmes M" first="Michaela" last="Kalmes">Michaela Kalmes</name></region><name sortKey="Blomeke, Brunhilde" sort="Blomeke, Brunhilde" uniqKey="Blomeke B" first="Brunhilde" last="Blömeke">Brunhilde Blömeke</name><name sortKey="Clemens, Judith" sort="Clemens, Judith" uniqKey="Clemens J" first="Judith" last="Clemens">Judith Clemens</name><name sortKey="Hennen, Jenny" sort="Hennen, Jenny" uniqKey="Hennen J" first="Jenny" last="Hennen">Jenny Hennen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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