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| Description
| - Aims. The aim was develop stable human cell line stable over-expressing transcription co-activator peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha) with restored hepatospecific functions and increased expression of major xenobiotic metabolizing enzymes. Methods. Six clones of HepG2-PGC-1 alpha and one control clone HepG2-pcDNA3 were isolated and analyzed for secretion of hepatospecific markers, fibrinogen, albumin and alpha1-antitrypsin. Expression levels of protein and mRNA of hepatocyte nuclear factor (HNF4 alpha), pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR) were determined. We measured basal and ligand inducible expression of CYP1A1 and CYP3A4. Results. Stably transfected cell line HepG2-PGC-1 alpha derived from HepG2 cells over-expressing PGC-1 alpha displayed increased secretion of fibrinogen, but not albumin or alpha1-antitrypsin compared to parent HepG2 cells. We found increased levels of HNF4 alpha, PXR and AhR proteins but not their mRNAs in HepG2-PGC1 cells. Basal expression of CYP3A4 protein in HepG2-PGC-1 alpha cells was increased but rifampicin-inducible expression of CYP3A4 protein was lowered in comparison with parent HepG2 cells. Induction of CYP3A4 mRNA varied between 1.3 - 1.9 fold in individual clones. Expression of TCDD-inducible CYP1A1 protein was lower in HepG2-PGC-1 alpha cells than in parent HepG2 cells. Induction of CYP1A1 mRNA by TCDD in HepG2-PGC-1 alpha cells was comparable with that in parent HepG2 cells and ranged between 103 - 198 fold. Conclusion. Stable expression of PGC-1 alpha in HepG2 cells restores several hepatospecific functions, such as secretion of fibrinogen, expression of HNF4 alpha 1 and xenoreceptors PXR and AhR. However, the expression and induction of key drug-metabolizing enzymes (CYP1A1 and CYP3A4) were not improved.
- Aims. The aim was develop stable human cell line stable over-expressing transcription co-activator peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha) with restored hepatospecific functions and increased expression of major xenobiotic metabolizing enzymes. Methods. Six clones of HepG2-PGC-1 alpha and one control clone HepG2-pcDNA3 were isolated and analyzed for secretion of hepatospecific markers, fibrinogen, albumin and alpha1-antitrypsin. Expression levels of protein and mRNA of hepatocyte nuclear factor (HNF4 alpha), pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR) were determined. We measured basal and ligand inducible expression of CYP1A1 and CYP3A4. Results. Stably transfected cell line HepG2-PGC-1 alpha derived from HepG2 cells over-expressing PGC-1 alpha displayed increased secretion of fibrinogen, but not albumin or alpha1-antitrypsin compared to parent HepG2 cells. We found increased levels of HNF4 alpha, PXR and AhR proteins but not their mRNAs in HepG2-PGC1 cells. Basal expression of CYP3A4 protein in HepG2-PGC-1 alpha cells was increased but rifampicin-inducible expression of CYP3A4 protein was lowered in comparison with parent HepG2 cells. Induction of CYP3A4 mRNA varied between 1.3 - 1.9 fold in individual clones. Expression of TCDD-inducible CYP1A1 protein was lower in HepG2-PGC-1 alpha cells than in parent HepG2 cells. Induction of CYP1A1 mRNA by TCDD in HepG2-PGC-1 alpha cells was comparable with that in parent HepG2 cells and ranged between 103 - 198 fold. Conclusion. Stable expression of PGC-1 alpha in HepG2 cells restores several hepatospecific functions, such as secretion of fibrinogen, expression of HNF4 alpha 1 and xenoreceptors PXR and AhR. However, the expression and induction of key drug-metabolizing enzymes (CYP1A1 and CYP3A4) were not improved. (en)
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| Title
| - Construction and characterization of peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 alpha over-expressing cell line derived from human hepatocyte carcinoma HepG2 cells)
- Construction and characterization of peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 alpha over-expressing cell line derived from human hepatocyte carcinoma HepG2 cells) (en)
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| skos:prefLabel
| - Construction and characterization of peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 alpha over-expressing cell line derived from human hepatocyte carcinoma HepG2 cells)
- Construction and characterization of peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1 alpha over-expressing cell line derived from human hepatocyte carcinoma HepG2 cells) (en)
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| skos:notation
| - RIV/00216208:11160/13:10146004!RIV14-GA0-11160___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - I, P(GAP304/10/0149), P(GAP503/10/0579), P(GBP303/12/G163), S
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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/00216208:11160/13:10146004
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - cytochrome P450; hepatocytes; cell lines; drug metabolism (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
| - Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
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| http://linked.open...in/vavai/riv/obor
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| 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
- Dořičáková, Aneta
- Novotná, Aneta
- Pávek, Petr
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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://bibframe.org/vocab/doi
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| http://localhost/t...ganizacniJednotka
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