Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33147782" target="_blank" >RIV/61989592:15310/13:33147782 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.if-pan.krakow.pl/pjp/pdf/2013/5_1322.pdf" target="_blank" >http://www.if-pan.krakow.pl/pjp/pdf/2013/5_1322.pdf</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes

Popis výsledku v původním jazyce

Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Its liver-specific expression in hepatocytes is strongly controlled by hepatocyte nuclear factor-4alfa (HNF4alfa). HNF4alfa expression and transcriptional activity have been demonstrated to be augmented by glucocorticoid receptor (GR) in human hepatocytes and rodent livers. It was examined whether GR activation indirectly induces OCT1 gene expression via HNF4alfa up-regulation in primary human hepatocytes. We also examined which other transcription factors are involved in OCT1 gene expression and whether they are regulated by dexamethasone using qRT-PCR and gene reporter assays. RESULTS: We found that dexamethasone significantly up-regulates OCT1 mRNA and protein in normal primary human hepatocytes, but not in hepatocyte-derived tumor cell lines HepG2 and MZ-Hep1. Consistently, we observed that HNF4alfa is induced by dexamethasone in primar

Název v anglickém jazyce

Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes

Popis výsledku anglicky

Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Its liver-specific expression in hepatocytes is strongly controlled by hepatocyte nuclear factor-4alfa (HNF4alfa). HNF4alfa expression and transcriptional activity have been demonstrated to be augmented by glucocorticoid receptor (GR) in human hepatocytes and rodent livers. It was examined whether GR activation indirectly induces OCT1 gene expression via HNF4alfa up-regulation in primary human hepatocytes. We also examined which other transcription factors are involved in OCT1 gene expression and whether they are regulated by dexamethasone using qRT-PCR and gene reporter assays. RESULTS: We found that dexamethasone significantly up-regulates OCT1 mRNA and protein in normal primary human hepatocytes, but not in hepatocyte-derived tumor cell lines HepG2 and MZ-Hep1. Consistently, we observed that HNF4alfa is induced by dexamethasone in primar

Druh

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

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Pharmacological Reports

ISSN

1734-1140

e-ISSN

—

Svazek periodika

65

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

PL - Polská republika

Počet stran výsledku

14

Strana od-do

1322-1335

Kód UT WoS článku

000330815700028

EID výsledku v databázi Scopus

—