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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F07%3A00003561%21RIV08-MSM-15110___
rdf:type
skos:Concept n14:Vysledek
dcterms:description
Cellular signaling by glucocorticoid receptor and aryl hydrocarbon receptor is restricted by microtubules interfering agents (MIAs). This leads to down-regulation of drug metabolizing enzymes and drug interactions. Here we investigated the effects of all-trans-retinoic acid (ATRA) and MIAs, i.e. colchicine, nocodazole and taxol on the regulation of retinoic acid receptor (RAR) genes in primary cultures of rat hepatocytes. ATRA (1 μM) down-regulated RARα and RARγ mRNAs (decrease 23% and 41%, respectively) whereas it up-regulated RARβ mRNA (4.3-fold induction). All MIAs diminished the expression of RARs in dose-dependent manner; the potency of MIAs increased in order NOC < COL < TAX and the extent of inhibition increased in order RARα < RARγ < RARβ. The levels of RARα protein were decreased by both MIAs and ATRA. The effects of ATRA were reversed by proteasome inhibitor MG-132, implying ligand-dependent RARα degradation. In contrast, the effects o Buněčná signalizace glukokortikoidním receptorem a aryl uhlovodíkovým receptorem je narušena látkami interferujícími s mikrotubuly (MIA). Následkem je down-regulace enzymů metabolizujících léčiva a lékové interakce. Zde jsme zkoumali účinky kyseliny all-trans retinové (ATRA) a MIA (tj. kolchicinu, nokodazolu, taxolu) na regulaci genů receptorů pro kyselinu retinovou (RAR) v primárních kulturách potkaních hepatocytů. ATRA způsobila pokles RARa a RARg mRNA (pokles 23% a 41%), zatímco obsah RARb mRNA byl zvýšen (4,3 krát). Všechny MIA způsobily koncentračně závislý pokles exprese RAR receptorů; účinnost MIA rostla v pořadí NOC<COL<TAX a míra inhibice rostla v pořadí RARa<RARg<RARb. Obsah RARa proteinu byl snížen působením MIA a ATRA. Účinky ATRA byly zvráceny inhibitorem proteasomu MG132, což ukazuje ligand-dependentní degradaci RARa receptoru. Na druhou stranu, účinky MIA byly nezávislé na proteasomu a pokles RARa byl způsoben spíše snížení genové exprese. Sledovali jsme transkripční aktivit Cellular signaling by glucocorticoid receptor and aryl hydrocarbon receptor is restricted by microtubules interfering agents (MIAs). This leads to down-regulation of drug metabolizing enzymes and drug interactions. Here we investigated the effects of all-trans-retinoic acid (ATRA) and MIAs, i.e. colchicine, nocodazole and taxol on the regulation of retinoic acid receptor (RAR) genes in primary cultures of rat hepatocytes. ATRA (1 μM) down-regulated RARα and RARγ mRNAs (decrease 23% and 41%, respectively) whereas it up-regulated RARβ mRNA (4.3-fold induction). All MIAs diminished the expression of RARs in dose-dependent manner; the potency of MIAs increased in order NOC < COL < TAX and the extent of inhibition increased in order RARα < RARγ < RARβ. The levels of RARα protein were decreased by both MIAs and ATRA. The effects of ATRA were reversed by proteasome inhibitor MG-132, implying ligand-dependent RARα degradation. In contrast, the effects o
dcterms:title
Expression, protein stability and transcriptional activity of retinoic acid receptors are affected by microtubules interfering agents and all-trans-retinoic acid in primary rat hepatocytes Exprese, stabilita proteinu a transkripční aktivity receptorů pro kyselinu retinovou v primárních potkaních hepatocytech jsou ovlivněny látkami narušujícími mikrotubuly a all-trans retinovou kyselinou Expression, protein stability and transcriptional activity of retinoic acid receptors are affected by microtubules interfering agents and all-trans-retinoic acid in primary rat hepatocytes
skos:prefLabel
Expression, protein stability and transcriptional activity of retinoic acid receptors are affected by microtubules interfering agents and all-trans-retinoic acid in primary rat hepatocytes Expression, protein stability and transcriptional activity of retinoic acid receptors are affected by microtubules interfering agents and all-trans-retinoic acid in primary rat hepatocytes Exprese, stabilita proteinu a transkripční aktivity receptorů pro kyselinu retinovou v primárních potkaních hepatocytech jsou ovlivněny látkami narušujícími mikrotubuly a all-trans retinovou kyselinou
skos:notation
RIV/61989592:15110/07:00003561!RIV08-MSM-15110___
n3:strany
89-96
n3:aktivita
n13:P n13:Z
n3:aktivity
P(GP303/04/P074), Z(MSM6198959216)
n3:cisloPeriodika
1-2
n3:dodaniDat
n11:2008
n3:domaciTvurceVysledku
n8:2514559 n8:4908171 n8:8069239
n3:druhVysledku
n15:J
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n19:predkladatel
n3:idSjednocenehoVysledku
421422
n3:idVysledku
RIV/61989592:15110/07:00003561
n3:jazykVysledku
n7:eng
n3:klicovaSlova
Retinoic acid receptors; Cellular signaling; Microtubules; Rat hepatocytes
n3:klicoveSlovo
n4:Cellular%20signaling n4:Microtubules n4:Retinoic%20acid%20receptors n4:Rat%20hepatocytes
n3:kodStatuVydavatele
IE - Irsko
n3:kontrolniKodProRIV
[2B489E1011C9]
n3:nazevZdroje
Molecular and Cellular Endocrinology
n3:obor
n17:CE
n3:pocetDomacichTvurcuVysledku
3
n3:pocetTvurcuVysledku
6
n3:projekt
n10:GP303%2F04%2FP074
n3:rokUplatneniVysledku
n11:2007
n3:svazekPeriodika
267
n3:tvurceVysledku
Dvořák, Zdeněk Vrzal, Radim Ondková, Slavomíra Ulrichová, Jitka Macejová, Dana Brtko, Július
n3:zamer
n18:MSM6198959216
s:issn
0303-7207
s:numberOfPages
8
n9:organizacniJednotka
15110