Transcriptional analysis of sodium valproate and lithium in a serotonergic cell line
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PROVIDER: PRJNA610734 | ENA |
REPOSITORIES: ENA
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Project description:Sodium valproate (VPA) and lithium are mood stabilizers, widely prescribed in the treatment of bipolar disorder, and yet the precise modes of therapeutic action for these drugs are not fully understood. After exposure of the rat serotonergic cell line RN46A to VPA, RNA-sequencing (RNA-Seq) analysis showed widespread changes in gene expression but no changes with lithium. Analysis by multiple pipelines revealed that as many as 230 genes were significantly upregulated and 72 genes were significantly downregulated in response to VPA exposure.
2020-03-07 | GSE146493 | GEO
Project description:This study provides an evaluation of changes in gene expression associated with sodium valproate treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (500 uM and 10 mM) of sodium valproate and water vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis.
2012-08-28 | GSE40338 | GEO
Project description:This study provides an evaluation of changes in gene expression associated with sodium valproate treatment of rat hepatocytes in vitro. Primary rat hepatocytes were treated for 24 and 48 hours with two doses (500 uM and 10 mM) of sodium valproate and water vehicle control. Five replicates of each treatment were performed. Cells were then extracted and RNA processed for microarray analysis. This series is part of a SuperSeries in which primary rat hepatocytes were treated with two doses of ten chemical compounds (and corresponding vehicle controls) for 24 and 48 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported. Time Course/Dose Response
2012-08-28 | E-GEOD-40338 | biostudies-arrayexpress
Project description:To explore the mechanism underlying anti-leukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated using the Annexin V/PI dual staining method. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed using gene expression microarray and validated by qRT-PCR. Gene ontology analysis was performed to establish the function of differentially expressed genes. The differentially expressed genes identified by using gene expression array were further used to query the CMAP database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis was observed in valproate exposed K562 cells using flow cytometry. A total of 706 transcripts were identified as being significantly differentially expressed. Eight differentially expressed genes that might be involved in apoptosis were verified by qRT-PCR. The significant enrichment analysis of gene ontology terms for the differentially expressed genes revealed that these genes are involved in many important biological processes such as apoptosis. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate observed in this study was most similar to that of HDACi and PI3K inhibitor in the connectivity map database, suggesting that sodium valproate might exert anti-leukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, the data obtained in this study might provide the ground for further studies to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment.
2011-11-11 | GSE32189 | GEO
Project description:To explore the mechanism underlying anti-leukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated using the Annexin V/PI dual staining method. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed using gene expression microarray and validated by qRT-PCR. Gene ontology analysis was performed to establish the function of differentially expressed genes. The differentially expressed genes identified by using gene expression array were further used to query the CMAP database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis was observed in valproate exposed K562 cells using flow cytometry. A total of 706 transcripts were identified as being significantly differentially expressed. Eight differentially expressed genes that might be involved in apoptosis were verified by qRT-PCR. The significant enrichment analysis of gene ontology terms for the differentially expressed genes revealed that these genes are involved in many important biological processes such as apoptosis. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate observed in this study was most similar to that of HDACi and PI3K inhibitor in the connectivity map database, suggesting that sodium valproate might exert anti-leukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, the data obtained in this study might provide the ground for further studies to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment. Gene expression in K562 cell line were measured after exposure to 2 mM valproate for 12 hours or left untreated as a control using Agilent SurePrint G3 Human GE 8x60K Microarray.
2011-11-11 | E-GEOD-32189 | biostudies-arrayexpress
Project description:The aim of this study is to determine the efficacy of combining the histone deacetylase (HDAC) inhibitor sodium valproate (VPA) with anti-EGFR monoclonal antibody (panitumumab or cetuximab) maintenance in the first-line treatment of patients with RAS wild type metastatic CRC.
| 5791 | ecrin-mdr-crc
Project description:We recently developed a fly model of pentylenetetrazol (PTZ)-induced long-term behavioral plasticity. Pharmacological validation suggests this model to be kindling-like. Hence, our model is of relevance in understanding the molecular pathogenesis of epileptogenesis as well as in screening potential antiepileptogenic agents. Sodium valproate (NaVP) is an antiepileptic drug, and in the process of developing our fly model we generated gene expression profile of flies’ head secondary to treatment of the insects with NaVP. Our results provide novel insights in to the drug’s mode of action. Keywords: Dose response
2007-10-05 | GSE7200 | GEO
Project description:The neurodegenerative disease Machado Joseph disease (MJD, also known as spinocerebellar ataxia-3) is a fatal disease that impairs control and co-ordination of movement. MJD is caused by expansion of a trinucleotide (CAG) repeat region within the ATXN3 gene, encoding a long polyglutamine (polyQ) region within the ataxin-3 protein. As transcription regulation is one of the functions of the ataxin-3 protein, weWe aimed to examine whether zebrafish expressing polyQ expanded ataxin-3 had altered levels of histone acetylation, and to establish test whether treatment with the histone deacetylase (HDAC) inhibitor sodium valproate was protective for the the first transgenic zebrafish.
2021-08-23 | PXD009612 | Pride
Project description:In the process of evaluating teratogenic properties of xenobiotica, the consumption of laboratory animals is high and costly which makes the development of alternative methods desirable. The pluripotent embryocarcinoma cell line P19, which closely resembles the early stage of an embryo, may be relevant as an in vitro model of teratogenicity. The antiepileptic drug Valproic acid (VPA) is a potent inducer of neural tube defects (ntd:s) in both human and mouse, but its mechanism of teratogenicity is not know. P19 cells were here treated with sodium valproate in a both time and dose dependent matter to profile the gene expression response with Codelink UniSet Mouse 20K I Bioarrays. This profile may reveal biomarkers of ntd:s as well as give mechanistic input of the teratogenicity of VPA.
2008-01-23 | E-MEXP-981 | biostudies-arrayexpress
Project description:Studying chemical disturbances during neural differentiation of mES cells has been established as an alternative in vitro testing approach for the identification of developmental toxicants. miRNAs represent a class of small regulatory RNA molecules, which bind to target mRNAs thereby repressing their translation. Many studies have shown an essential role of miRNAs in regulation of gene expression during development and ESC differentiation. Thus, neural differentiation of ESC in vitro allows investigating the role of miRNAs in chemical-mediated developmental toxicity. We analyzed the expression of miRNAs and transcriptomics changes during neural differentiation of mESC exposed to the developmental neurotoxicant sodium valproate (VPA). A total of 110 miRNAs and 377 mRNAs were identified differently expressed in neural differentiating mES cells under VPA treatment (300µM) compared to solvent control on day 16 of differentiation. Analysis of miRNA expression revealed that valproate switches the lineage specification from neural to myogenic differentiation (upregulation of muscle-enriched miRNAs mir-206, mir-133a and mir-10a and downregulation of neuro-specific miRNAs mir-124a, mir-128 and mir-137). The findings on the miRNA level could be confirmed on mRNA level (induction of expression of myogenic regulatory factors (MRFs) as well as muscle specific genes (Actc1, calponin, myosin light chain, asporin, decorin) and repression of genes involved in neurogenesis (Otx1 and 2, Zic3, 4, 5)) as well as morphologically by immunocytochemistry. The observed results were VPA specific and most probably due to inhibition of histone deacetylase (HDAC) activity of VPA for two reasons: (i) we did not observe any induction of muscle specific miRNAs in neural differentiating ES cells exposed to the unrelated developmental neurotoxicant sodium arsenite; (ii) expression of muscle specific mir-206 and muscle enriched mir-10a was similarly increased in cells exposed to a structurally different HDAC inhibitor, trichostatin A (TSA). Furthermore, using our in vitro cell system we could confirm an aberrant expression of known VPA target genes and genes involved in neural tube closure. We conclude that miRNA expression profiling is a suitable molecular endpoint for developmental neurotoxicity. Observed lineage shift into myogenesis, where miRNAs play a significant role, could be a major developmental neurotoxical mechanism of VPA. We used microarray approach to identify altered miRNA expression in neural differentiated mES cells exposed to two known developmental neurotxicants and epigenetic active substances, sodium valproate (VPA) and sodium arsenite (As)
2016-08-01 | GSE50216 | GEO