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| Description
| - 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 primary human hepatocytes, but not in hepatocyte tumor-derived cell lines. Viral transduction of MZ-Hep1 cells with the expression constructs for HNF4alfa, CCAAT/enhancer binding proteins beta (C/EBPbeta) and peroxisome proliferator-activated receptor-gama coactivator 1alfa (PGC1alfa) demonstrated significant roles of the transcription factors in OCT1 gene regulation. We found that expression of OCT1 mRNA in human livers significantly correlates with C/EBPbeta and HNF4alfa mRNAs expression and that C/EBPbeta co-transfection stimulates OCT1 gene reporter construct in HepG2 cells. Nevertheless, neither C/EBPbeta nor PGC1alfa were upregulated in human hepatocytes by dexamethasone. CONCLUSION: We can conclude that GR-induced expression of HNF4alfa may contribute to indirect OCT1 gene up-regulation by dexamethasone in primary human hepatocytes, but not in hepatocyte-derived tumor cell lines.
- 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 primary human hepatocytes, but not in hepatocyte tumor-derived cell lines. Viral transduction of MZ-Hep1 cells with the expression constructs for HNF4alfa, CCAAT/enhancer binding proteins beta (C/EBPbeta) and peroxisome proliferator-activated receptor-gama coactivator 1alfa (PGC1alfa) demonstrated significant roles of the transcription factors in OCT1 gene regulation. We found that expression of OCT1 mRNA in human livers significantly correlates with C/EBPbeta and HNF4alfa mRNAs expression and that C/EBPbeta co-transfection stimulates OCT1 gene reporter construct in HepG2 cells. Nevertheless, neither C/EBPbeta nor PGC1alfa were upregulated in human hepatocytes by dexamethasone. CONCLUSION: We can conclude that GR-induced expression of HNF4alfa may contribute to indirect OCT1 gene up-regulation by dexamethasone in primary human hepatocytes, but not in hepatocyte-derived tumor cell lines. (en)
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| Title
| - Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes
- Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes (en)
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| skos:prefLabel
| - Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes
- Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4alfa upregulation in primary human hepatocytes (en)
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| skos:notation
| - RIV/61989592:15310/13:33147782!RIV14-GA0-15310___
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| http://linked.open...avai/predkladatel
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - P(GAP303/12/0472), P(GBP303/12/G163)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/61989592:15310/13:33147782
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| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - hepatocytes; human; primary; upregulation; HNF4alfa; via; expression; SLC22A1; OCT1; transporter; cation; organic; regulates; receptor; Glucocorticoid (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
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| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Dvořák, Zdeněk
- Pávek, Petr
- Vrzal, Radim
- Krausová, Lucie
- Rulcová, Alice
- Jover, Ramiro
- Smutný, Tomáš
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| http://linked.open...ain/vavai/riv/wos
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| issn
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| number of pages
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| http://localhost/t...ganizacniJednotka
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