About: Valproate activates ERK signaling pathway in primary human hepatocytes

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An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://biomed.papers.upol.cz/pdfs/bio/2014/01/06.pdf
Description	Aim. Valproic acid (VPA) is a widely-used anticonvulsant and mood-stabilizing agent. VPA is also known to inhibit histone deacetylases (HDACs) affecting the expression of numerous genes. Methods. In the present study, we examined the effect of VPA on the extracellular signal-related kinase (ERK, p42/p44) pathway (Ras-Raf-MEK-ERK) belonging to the mitogen-activated protein kinases (MAPKs) pathways in primary human hepatocytes. In the liver, the pathway is associated with progression of hepatocellular carcinoma. Results. We found that VPA in a therapeutically relevant concentration (500 M) activates the ERK pathway, as indicated by increased ERK Thr202/Tyr204 phosphorylation. Interestingly, a prototype HDAC inhibitor, trichostatin A, also activated ERK phosphorylation in primary human hepatocytes. These data suggest that HDAC inhibition might be the primary stimulus for ERK pathway activation in primary human hepatocytes. Notably, U0126, a MEK1 inhibitor, was ineffective in inhibiting ERK pathway activation, likely due to its metabolic deactivation in metabolically competent primary human hepatocytes. Conclusion. We conclude that VPA activates the ERK pathway in primary human hepatocytes. Aim. Valproic acid (VPA) is a widely-used anticonvulsant and mood-stabilizing agent. VPA is also known to inhibit histone deacetylases (HDACs) affecting the expression of numerous genes. Methods. In the present study, we examined the effect of VPA on the extracellular signal-related kinase (ERK, p42/p44) pathway (Ras-Raf-MEK-ERK) belonging to the mitogen-activated protein kinases (MAPKs) pathways in primary human hepatocytes. In the liver, the pathway is associated with progression of hepatocellular carcinoma. Results. We found that VPA in a therapeutically relevant concentration (500 M) activates the ERK pathway, as indicated by increased ERK Thr202/Tyr204 phosphorylation. Interestingly, a prototype HDAC inhibitor, trichostatin A, also activated ERK phosphorylation in primary human hepatocytes. These data suggest that HDAC inhibition might be the primary stimulus for ERK pathway activation in primary human hepatocytes. Notably, U0126, a MEK1 inhibitor, was ineffective in inhibiting ERK pathway activation, likely due to its metabolic deactivation in metabolically competent primary human hepatocytes. Conclusion. We conclude that VPA activates the ERK pathway in primary human hepatocytes. (en)
Title	Valproate activates ERK signaling pathway in primary human hepatocytes Valproate activates ERK signaling pathway in primary human hepatocytes (en)
skos:prefLabel	Valproate activates ERK signaling pathway in primary human hepatocytes Valproate activates ERK signaling pathway in primary human hepatocytes (en)
skos:notation	RIV/00216208:11160/14:10282293!RIV15-MSM-11160___
http://linked.open...avai/riv/aktivita	I P S
http://linked.open...avai/riv/aktivity	I, P(GBP303/12/G163), S
http://linked.open...iv/cisloPeriodika	1
http://linked.open...vai/riv/dodaniDat	2015
http://linked.open...aciTvurceVysledku	Pávek, Petr Bitman, Michal
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Karlova v Praze / Farmaceutická fakulta v Hradci Králové
http://linked.open...dnocenehoVysledku	52928
http://linked.open...ai/riv/idVysledku	RIV/00216208:11160/14:10282293
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	cellular signaling; ERK pathway; valproic acid (en)
http://linked.open.../riv/klicoveSlovo	cellular signaling valproic acid ERK pathway
http://linked.open...odStatuVydavatele	CZ - Česká republika
http://linked.open...ontrolniKodProRIV	[E817718EA77C]
http://linked.open...i/riv/nazevZdroje	Biomedical Papers
http://linked.open...in/vavai/riv/obor	FR
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	4 (xsd:int)
http://linked.open...vavai/riv/projekt	Centre of drug-dietary supplements interactions and nutrigenetics
http://linked.open...UplatneniVysledku	2014
http://linked.open...v/svazekPeriodika	158
http://linked.open...iv/tvurceVysledku	Dvořák, Zdeněk Pávek, Petr Vrzal, Radim Bitman, Michal
http://linked.open...ain/vavai/riv/wos	000338627400007
issn	1213-8118
number of pages	5 (xsd:int)
http://bibframe.org/vocab/doi	10.5507/bp.2012.038
http://localhost/t...ganizacniJednotka	11160

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