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Role of the transcription factor Nur77 (Nr4a1) in the effects of antipsychotic drugs

ABSTRACT: Role of the transcription factor Nur77 (Nr4a1) in the effects of antipsychotic drugs

PROVIDER: PRJNA945096 | ENA |

REPOSITORIES: ENA

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Role of the transcription factor Nur77 (Nr4a1) in the effects of antipsychotic drugs

Project description:To better understand the role of Nur77 in antipsychotic drug effects we performed a transcriptional analysis (RNAseq) to compare gene expression patterns between wild type and Nur77-deficient rats exposed to haloperidol.

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Classification of Antipsychotic Drugs by Gene Expression in the Frontal Cortex of Mice

Project description:Antipsychotic drugs are classified as typical and atypical based on extrapyramidal effects. However, since the frontal cortex is one of the most important regions for antipsychotic actions, this study attempted to classify antipsychotic drugs based on gene expression in the frontal cortex. Chlorpromazine and thioridazine were selected as typical antipsychotics, and olanzapine and quetiapine as atypical antipsychotics. Since these drugs have similar chemical structures, the effect of the basic structure on gene expression can be eliminated. Cluster analysis of microarray experiments showed thioridazine and olanzapine constituted a robust cluster. K-means clustering separated 4-drug-administered mice into chlorpromazine-quetiapine and thioridazine-olanzapine groups. This classification scheme is different from that which is based on criteria currently used to group the typical and atypical drugs and suggests that antipsychotic drugs can be further separated into multiple groups. Keywords: repeat sample

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Regulation of Ag-activated B cells by Nur77/Nr4a1

Project description:Regulation of Ag-activated B cells by Nur77/Nr4a1

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The orphan nuclear receptor NR4A1 (Nur77, TR3) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells

Project description:NR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer cells and tumors and exhibits pro-oncogenic activity. Knockdown of NR4A1 by RNA interference (siNR4A1) in Panc1 cells and analysis of the proteome resulted in induction of several markers of endoplasmic reticulum (ER) stress including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), activating transcription factor-3 (ATF-3) and AFT-6. These effects were accompanied by induction of apoptosis and similar results were observed after treatment of pancreatic cancer cells with the known inactivator of NR4A1, 1,1-bis(3’-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH). Both siNR4A1 (transfected) and DIM-C-pPhOH also induced reactive oxygen species (ROS) and induction of ROS and ER stress by these agents was attenuated after cotreatment with antioxidants. Transfection of Panc1 cells with siNR4A1 follow by analysis of gene expression by arrays identified ROS metabolism genes regulated by NR4A1. Knockdown of one of these genes, thioredoxin domain containing 5 (TXNDC5) also resulted in induction of ROS and ER stress demonstrating that NR4A1 regulates levels of ER stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Inactivation of this receptor by siNR4A1 or DIM-C-pPhOH decreases TXNDC5 resulting in activation of ROS/ER stress and pro-apoptotic pathways and represents a novel pathway for inducing cell death in pancreatic cancer cells. Two groups of samples are included: 1. siControl; 2. siNR4A1 treatment in PAC1 cell. Transfection of Panc1 cells with siNR4A1 follow by analysis of gene expression by arrays identified ROS metabolism genes regulated by NR4A1.

2014-04-30 | E-GEOD-46994 | biostudies-arrayexpress

Understanding pharmaco-epigenomic response of antipsychotic drugs using genome-wide microRNA expression profile in liver cell line

Project description:The study is directed to understand the impact of antipsychotic drugs on miRNA expression in liver cell line model

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Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance

Project description:The nuclear orphan receptor Nur77 (NR4A1, TR3, or NGFI-B) has been shown to exhibit an anti-inflammatory function in macrophages. To further elucidate the role of Nur77 in macrophage physiology, we compared the transcriptome of bone marrow-derived macrophages (BMM) from wild-type (WT) and Nur77-knockout (KO) mice both before and after stimulation with IL4 or LPS. Comparison of gene expression in bone marrow-derived macrophages, isolated from 3 wild-type (control) and 3 Nur77-/- mice (case), left untreated or stimulated in triplicate for 8 hours with LPS or IL-4

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The orphan nuclear receptor NR4A1 (Nur77, TR3) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells

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Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance

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Altered transcriptional programming in Nur77-GFPhi naïve CD8 T cells

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2023-03-02 | GSE223457 | GEO

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