Rifampicin Does not Significantly Affect the Expression of Small Heterodimer Partner in Primary Human Hepatocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F12%3A33142723" target="_blank" >RIV/61989592:15310/12:33142723 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/12:10124924

Výsledek na webu

<a href="http://www.frontiersin.org/Drug_Metabolism_and_Transport/10.3389/fphar.2012.00001/full" target="_blank" >http://www.frontiersin.org/Drug_Metabolism_and_Transport/10.3389/fphar.2012.00001/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2012.00001" target="_blank" >10.3389/fphar.2012.00001</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Rifampicin Does not Significantly Affect the Expression of Small Heterodimer Partner in Primary Human Hepatocytes

Popis výsledku v původním jazyce

The small/short heterodimer partner (SHP, NR0B2) is a nuclear receptor corepressor lacking a DNA binding domain. SHP is induced by bile acid-activated farnesoid X receptor (FXR) resulting in CYP7A1 gene suppression. In contrast, Pregnane X receptor (PXR)activation by its ligands was recently suggested to inhibit SHP gene transactivation to maximize the induction of PXR target genes. However, there are also conflicting reports in literature whether PXR or rodent Pxr activation down-regulates SHP/Shp expression. Moreover, the PXR-mediated regulation of the SHP gene has been studied only at the SHP mRNA and transactivation (gene reporter assay) levels. In this study, we studied the effect of rifampicin, a prototype PXR ligand, on SHP mRNA, and protein expression in three primary human hepatocyte cultures. We found that SHP mRNA is not systematically down-regulated in hepatocyte in culture after 24 h treatment with rifampicin. Consistently, we did not observe down-regulation of SHP protei

Název v anglickém jazyce

Rifampicin Does not Significantly Affect the Expression of Small Heterodimer Partner in Primary Human Hepatocytes

Popis výsledku anglicky

The small/short heterodimer partner (SHP, NR0B2) is a nuclear receptor corepressor lacking a DNA binding domain. SHP is induced by bile acid-activated farnesoid X receptor (FXR) resulting in CYP7A1 gene suppression. In contrast, Pregnane X receptor (PXR)activation by its ligands was recently suggested to inhibit SHP gene transactivation to maximize the induction of PXR target genes. However, there are also conflicting reports in literature whether PXR or rodent Pxr activation down-regulates SHP/Shp expression. Moreover, the PXR-mediated regulation of the SHP gene has been studied only at the SHP mRNA and transactivation (gene reporter assay) levels. In this study, we studied the effect of rifampicin, a prototype PXR ligand, on SHP mRNA, and protein expression in three primary human hepatocyte cultures. We found that SHP mRNA is not systematically down-regulated in hepatocyte in culture after 24 h treatment with rifampicin. Consistently, we did not observe down-regulation of SHP protei

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/GA303%2F07%2F0128" target="_blank" >GA303/07/0128: Transkripční regulační mechanizmy vybraných cytochromů P-450 a lékových transportérů v extrahepatálních tkáních a jejich vzájemné interakce.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2012

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

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Svazek periodika

3

Číslo periodika v rámci svazku

Leden 2012

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

5

Strana od-do

1-5

Kód UT WoS článku

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EID výsledku v databázi Scopus

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