This HTML5 document contains 46 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

PrefixIRI
dctermshttp://purl.org/dc/terms/
n17http://localhost/temp/predkladatel/
n15http://linked.opendata.cz/resource/domain/vavai/riv/tvurce/
n11http://linked.opendata.cz/resource/domain/vavai/subjekt/
n10http://linked.opendata.cz/ontology/domain/vavai/
n20http://linked.opendata.cz/resource/domain/vavai/zamer/
shttp://schema.org/
skoshttp://www.w3.org/2004/02/skos/core#
n8http://linked.opendata.cz/resource/domain/vavai/vysledek/RIV%2F00216208%3A11150%2F11%3A10105145%21RIV12-MSM-11150___/
rdfshttp://www.w3.org/2000/01/rdf-schema#
n3http://linked.opendata.cz/ontology/domain/vavai/riv/
n5http://bibframe.org/vocab/
n2http://linked.opendata.cz/resource/domain/vavai/vysledek/
rdfhttp://www.w3.org/1999/02/22-rdf-syntax-ns#
n4http://linked.opendata.cz/ontology/domain/vavai/riv/klicoveSlovo/
n19http://linked.opendata.cz/ontology/domain/vavai/riv/duvernostUdaju/
xsdhhttp://www.w3.org/2001/XMLSchema#
n18http://linked.opendata.cz/ontology/domain/vavai/riv/aktivita/
n9http://linked.opendata.cz/ontology/domain/vavai/riv/jazykVysledku/
n21http://linked.opendata.cz/ontology/domain/vavai/riv/obor/
n13http://linked.opendata.cz/ontology/domain/vavai/riv/druhVysledku/
n14http://reference.data.gov.uk/id/gregorian-year/

Statements

Subject Item
n2:RIV%2F00216208%3A11150%2F11%3A10105145%21RIV12-MSM-11150___
rdf:type
n10:Vysledek skos:Concept
rdfs:seeAlso
http://www.sciencedirect.com/science/article/pii/S0378427411001949
dcterms:description
Zinc pyrithione is used as a topical agent in a range of medicinal and cosmetic applications. Despite its extensive use and reported beneficial effects in treatment of various dermal problems, its potential toxicity towards skin cells remains relatively underexplored. In this work we investigated effects of nM zinc pyrithione on cell stress response pathways of primary human skin fibroblasts during 24 h of exposure. We demonstrate that zinc pyrithione-induced cytotoxity in dermal fibroblasts is dose-dependent and it associates with increased intracellular zinc concentrations and activated stress response pathways including p53 and stress kinase p38. Higher zinc pyrithione concentrations (500 nM and above) stimulate oxidative stress and moderate DNA damage which occur in the presence of activated p38 kinase. Cells further upregulate the expression of p53 which increases its transcriptional activity while mitogenic signaling exemplified by mTOR (mammalian target of rapamycin) expression is suppressed and these steps lead to mitochondrial, caspase-dependent apoptosis. Conversely, lower zinc concentrations (125 nM) fail to induce oxidative stress and significant DNA damage; however, treated cells still activate p38 and upregulate the expression and transcriptional activity of p53 and its target gene p21 as well as the expression of p16 in the presence of active mTOR pathway and a changed DNA methylation pattern. The end result is premature senescence phenotype. Specific pharmacological inhibitors as well as gene knockdown technology prove that an interaction between p38, p53 and mTOR might be responsible for these observed endpoints. Taken together, exposure of dermal fibroblasts to varying concentrations of zinc pyrithione may result in either cell death-apoptosis or cellular premature senescence which attests to the ability of this compound to affect this type of cells in an in vitro model system. Zinc pyrithione is used as a topical agent in a range of medicinal and cosmetic applications. Despite its extensive use and reported beneficial effects in treatment of various dermal problems, its potential toxicity towards skin cells remains relatively underexplored. In this work we investigated effects of nM zinc pyrithione on cell stress response pathways of primary human skin fibroblasts during 24 h of exposure. We demonstrate that zinc pyrithione-induced cytotoxity in dermal fibroblasts is dose-dependent and it associates with increased intracellular zinc concentrations and activated stress response pathways including p53 and stress kinase p38. Higher zinc pyrithione concentrations (500 nM and above) stimulate oxidative stress and moderate DNA damage which occur in the presence of activated p38 kinase. Cells further upregulate the expression of p53 which increases its transcriptional activity while mitogenic signaling exemplified by mTOR (mammalian target of rapamycin) expression is suppressed and these steps lead to mitochondrial, caspase-dependent apoptosis. Conversely, lower zinc concentrations (125 nM) fail to induce oxidative stress and significant DNA damage; however, treated cells still activate p38 and upregulate the expression and transcriptional activity of p53 and its target gene p21 as well as the expression of p16 in the presence of active mTOR pathway and a changed DNA methylation pattern. The end result is premature senescence phenotype. Specific pharmacological inhibitors as well as gene knockdown technology prove that an interaction between p38, p53 and mTOR might be responsible for these observed endpoints. Taken together, exposure of dermal fibroblasts to varying concentrations of zinc pyrithione may result in either cell death-apoptosis or cellular premature senescence which attests to the ability of this compound to affect this type of cells in an in vitro model system.
dcterms:title
Stress responses of human dermal fibroblasts exposed to zinc pyrithione Stress responses of human dermal fibroblasts exposed to zinc pyrithione
skos:prefLabel
Stress responses of human dermal fibroblasts exposed to zinc pyrithione Stress responses of human dermal fibroblasts exposed to zinc pyrithione
skos:notation
RIV/00216208:11150/11:10105145!RIV12-MSM-11150___
n10:predkladatel
n11:orjk%3A11150
n3:aktivita
n18:Z
n3:aktivity
Z(MSM0021620820)
n3:cisloPeriodika
2-3
n3:dodaniDat
n14:2012
n3:domaciTvurceVysledku
n15:1249746 n15:2650673
n3:druhVysledku
n13:J
n3:duvernostUdaju
n19:S
n3:entitaPredkladatele
n8:predkladatel
n3:idSjednocenehoVysledku
232631
n3:idVysledku
RIV/00216208:11150/11:10105145
n3:jazykVysledku
n9:eng
n3:klicovaSlova
DNA damage; Dermal fibroblasts; Premature senescence; In vitro; p53; Zinc pyrithione
n3:klicoveSlovo
n4:Dermal%20fibroblasts n4:DNA%20damage n4:Zinc%20pyrithione n4:Premature%20senescence n4:In%20vitro n4:p53
n3:kodStatuVydavatele
NL - Nizozemsko
n3:kontrolniKodProRIV
[CD9265E742F4]
n3:nazevZdroje
Toxicology Letters
n3:obor
n21:EB
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
2
n3:rokUplatneniVysledku
n14:2011
n3:svazekPeriodika
204
n3:tvurceVysledku
Červinka, Miroslav Rudolf, Emil
n3:wos
000292475900009
n3:zamer
n20:MSM0021620820
s:issn
0378-4274
s:numberOfPages
11
n5:doi
10.1016/j.toxlet.2011.04.028
n17:organizacniJednotka
11150