Impact of the arylhydrocarbon receptor on eugenol- and isoeugenol-induced cell cycle arrest in human immortalized keratinocytes (HaCaT)

Kalmes, Michaela; Neumeyer, Andrea; Rı́o, Paula; Fritsche, Ellen; Blömeke, Brunhilde

doi:10.1515/bc.2006.148

Cited by 24 publications

(10 citation statements)

References 38 publications

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“…17 In contrast to control cell, which carry the parental (empty) lentiviral expression vector (e.v. ), no AhR protein was detectable in the knockdown (k.d.)…”

Section: Resultsmentioning

confidence: 99%

“…Lentiviral transduced HaCaT cells, containing either shRNA sequences for AhR silencing or nonsilencing, are described elsewhere. 17 Primary human keratinocytes (i.e., NHEKs) were isolated from foreskin tissue samples by overnight trypsin digestion. The culture medium was a 3 : 1 mixture of Ham's F-12 medium (L-glutamine (2 mM) and penicillin/streptomycin (100 U/ml)) and DMEM (low glucose (1 g/l), L-glutamine (8 mM) and penicillin/streptomycin (100 U/ml)), supplemented with adenine, insulin, fetal calf serum, hydrocortisone, epidermal growth factor and forskoline.…”

Section: Methodsmentioning

confidence: 99%

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Activation of the aryl hydrocarbon receptor sensitises human keratinocytes for CD95L- and TRAIL-induced apoptosis

et al. 2012

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In this study, we have analysed the apoptotic effects of the ubiquitous environmental toxin benzo[a]pyrene (BP) in HaCaT cells and human keratinocytes. Although prolonged exposure to BP was not cytotoxic on its own, a strong enhancement of CD95 (Fas)-mediated apoptosis was observed with BP at concentrations activating the aryl hydrocarbon receptor (AhR). Importantly, the ultimately mutagenic BP-metabolite, that is, (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE), failed to enhance CD95-mediated cell death, suggesting that the observed pro-apoptotic effect of BP is neither associated with DNA adducts nor DNA-damage related signalling. CD95-induced apoptosis was also enhanced by β-naphtoflavone, a well-known agonist of the AhR that does not induce DNA damage, thus suggesting a crucial role for AhR activation. Consistently, BP failed to sensitise for CD95L-induced apoptosis in AhR knockdown HaCaT cells. Furthermore, inhibition of CYP1A1 and/or 1B1 expression did not affect the pro-apoptotic crosstalk. Exposure to BP did not increase expression of CD95, but led to augmented activation of caspase-8. Enhancement of apoptosis was also observed with the TRAIL death receptors that activate caspase-8 and apoptosis by similar mechanisms as CD95. Together, these observations indicate an interference of AhR signalling with the activity of receptor-associated signalling intermediates that are shared by CD95 and TRAIL receptors. Our data thus suggest that AhR agonists can enhance cytokine-mediated adversity upon dermal exposure.

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“…17 In contrast to control cell, which carry the parental (empty) lentiviral expression vector (e.v. ), no AhR protein was detectable in the knockdown (k.d.)…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Activation of the aryl hydrocarbon receptor sensitises human keratinocytes for CD95L- and TRAIL-induced apoptosis

et al. 2012

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“…Environmental chemicals, including contact allergens, are known to shift cell-cycle phases (Kalmes et al, 2006) and, although not yet shown for NAT1, some enzymes including those involved in xenobiotic biotransformation (Gilroy et al, 2001) are expressed cell-cycle phase-dependently. Therefore, we first studied NAT1 activities in different cell-cycle phases and further analyzed cell-cycle phase distribution after PPD treatment.…”

Section: Ppd Inhibits Nat1 In Keratinocytes 321mentioning

confidence: 99%

Characterization of N-Acetyltransferase 1 Activity in Human Keratinocytes and Modulation by para-Phenylenediamine

Bonifas

Scheitza²,

Clemens³

et al. 2010

J Pharmacol Exp Ther

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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 phasedependent. 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 M) 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.

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“…30 The vector, harvest of recombinant lentiviral particles, and infection of skin fibroblasts were performed as previously described. 30 HA concentration in the supernatant of human skin fibroblasts was determined by using HA enzyme-linked immunosorbent assay (Corgenix) 5 days after infection and was calculated as ratio of HA and total cellular protein.…”

Section: Lentiviral Shrna Expressionmentioning

confidence: 99%

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

Dai

Freudenberger

Zipper

et al. 2007

The American Journal of Pathology

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142

116

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Remodeling of the dermal extracellular matrix occurs during photoaging. Here, the effect of repetitive UVB irradiation on dermal hyaluronic acid (HA) was examined. C57/BL6 mice were chronically (182 days) irradiated with UVB, and consecutive skin biopsies were collected during the irradiation period and afterward (300 and 400 days of age). UVB caused marked loss of HA from the papillary dermis and down-regulation of HA synthase 1 (HAS1), HAS2, and HAS3 mRNA expression. In contrast, hyaluronidases (HYAL) 1, HYAL2, and HA receptor CD44 were unchanged. Furthermore, transforming growth factor ␤-1 (TGF-␤1) and TGF-␤1-receptor II expression were decreased in UVB-irradiated biopsies, and TGF-␤1 strongly induced HAS1 and HAS2 expression in cultured dermal fibroblasts. Therefore, TGF-␤1 might be one factor involved in UVB-induced down-regulation of HAS enzymes. In addition, total cell number and the percentage of proliferating fibroblasts in the papillary dermis of UVB-irradiated mice were decreased. Down-regulation of HAS2 by lentiviral overexpression of short hairpin RNA in vitro caused inhibition of HA synthesis, DNA synthesis, and migration of dermal fibroblasts. In conclusion, chronic UVB irradiation induces loss of HA from the dermis, thereby contributing to the quiescent phenotype of dermal fibroblasts. 1 Photoaging is the most common form of skin damage caused by chronic, repetitive sun exposure.2 The long-term exposure to solar UV irradiation induces damage to the dermal connective tissue and the extracellular matrix (ECM), which in turn leads to the aged appearance of photodamaged skin. Hallmark of this UV-induced ECM remodeling is the degradation of collagen and elastin through the UVB-induced activation of matrix metalloproteinases and decreased de novo synthesis of collagen. The mechanisms of UVB-induced matrix metalloproteinase activation 3 and inhibition of collagen synthesis have been studied in detail.2 In contrast the effect of UVB on hyaluronic acid (HA), another key component of the dermal ECM, is much less understood, and the underlying mechanisms are primarily unknown. HA is a linear polymer composed of repeating disaccharides (D-glucuronic acid-␤-1,3-N-acetylglucosamine-␤-1,4-) and assembled from the respective activated nucleotide sugars (UDPglucuronic acid, UDP-N-acetylglucosamine) at the inner plasma membrane by HA synthases (HAS). Three different HAS isoforms are known that reside in the plasma membrane and extrude the growing HA polymer into the extracellular space.4 HAS1 and HAS2 produce high molecular mass HA (2 to 4 ϫ 10 6 Da), whereas HAS3 synthesizes smaller HA (0.4 to 2.5 ϫ 10 5 Da). 5 The variation of the MW is the only modification of HA because O-or N-sulfations do not occur. HA is an agonist of CD44 and RHAMM (receptor of HA-mediated motility), which enables HA to initiate specific signaling events.6 This receptor signaling and the formation of pericellular HA coats supports proliferation and migration of a variety of cell types including skin fibroblasts. 7 In addition, antiapoptoti...

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Impact of the arylhydrocarbon receptor on eugenol- and isoeugenol-induced cell cycle arrest in human immortalized keratinocytes (HaCaT)

Cited by 24 publications

References 38 publications

Activation of the aryl hydrocarbon receptor sensitises human keratinocytes for CD95L- and TRAIL-induced apoptosis

Activation of the aryl hydrocarbon receptor sensitises human keratinocytes for CD95L- and TRAIL-induced apoptosis

Characterization of N-Acetyltransferase 1 Activity in Human Keratinocytes and Modulation by para-Phenylenediamine

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

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