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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

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F07%3A00003561" target="_blank" >RIV/61989592:15110/07:00003561 - isvavai.cz</a>

  • Result on the web

  • DOI - Digital Object Identifier

Alternative languages

  • Result language

    angličtina

  • Original language name

    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

  • Original language 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 ?M) down-regulated RAR? and RAR? mRNAs (decrease 23% and 41%, respectively) whereas it up-regulated RAR? 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 RAR? < RAR? < RAR?. Thelevels of RAR? protein were decreased by both MIAs and ATRA. The effects of ATRA were reversed by proteasome inhibitor MG-132, implying ligand-dependent RAR? degradation. In contrast, the effects o

  • Czech name

    Exprese, stabilita proteinu a transkripční aktivity receptorů pro kyselinu retinovou v primárních potkaních hepatocytech jsou ovlivněny látkami narušujícími mikrotubuly a all-trans retinovou kyselinou

  • Czech description

    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 akt

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    CE - Biochemistry

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/GP303%2F04%2FP074" target="_blank" >GP303/04/P074: Effect of pro- and anti-inflammatory factors on cytochrome P450 expression - modulation by natural substances</a><br>

  • Continuities

    Z - Vyzkumny zamer (s odkazem do CEZ)

Others

  • Publication year

    2007

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Molecular and Cellular Endocrinology

  • ISSN

    0303-7207

  • e-ISSN

  • Volume of the periodical

    267

  • Issue of the periodical within the volume

    1-2

  • Country of publishing house

    IE - IRELAND

  • Number of pages

    8

  • Pages from-to

    89-96

  • UT code for WoS article

  • EID of the result in the Scopus database