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PROVIDER: PRJNA511485 | ENA |
REPOSITORIES: ENA
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Project description:Effects of environmental enrichment on postnatal mouse cortex regulome
| PRJNA480164 | ENA
Project description:The inhibition of DYRK1A (Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A) activity, triplicated in trisomy 21 subjects, has been proved as a promising therapy for Down syndrome. Epigallocatechin-3-gallate (EGCG), a polyphenol of green tea, is an allosteric inhibitor of DYRK1A that showed beneficial pro-cognitive effects in clinical trials with DS individuals. However, EGCG induces several pharmacological effects, and there is no proof that the observed improvements result from DYRK1A inhibition. Besides, the direct consequences of Dyrk1A overexpression are not well defined. We therefore used quantitative proteomics to decipher the proteome and phosphoproteome alterations resulting from Dyrk1A overexpression and its inhibition to get insight into the mechanism of action of EGCG. Towards this aim, we used mice overexpressing Dyrk1A, and compared the hippocampal proteome and phosphoproteome with their wild type counterparts, in basal conditions, and after treatment with EGCG. Moreover, given that the human clinical trials found that the effects of EGCG potentiated the effects of cognitive stimulation, we also included in our study treatment with environmental enrichment and its combination with EGCG. We found that DYRK1A overexpression leads to alterations in protein and phosphoprotein levels of hundreds of proteins, and that the levels of proteins involved in key postsynaptic pathways are restored by the cognitive enhancer treatments, which could help conceiving new therapeutic strategies.
2019-12-11 | PXD010689 | Pride
Project description:Down syndrome is the main genetic cause of intellectual disability and is due to triplication of human chromosome 21 (HSA21). Green tea extracts containing epigallocatechin-3-gallate (green tea) improve cognition both in mouse models and individuals with Down syndrome. We here analyzed the proteome and phosphoproteome alterations in a Down syndrome mouse model, the partial trisomic Ts65Dn mice, and the effect produced by the green tea extract and environmental enrichment (EE). Trisomic hippocampi presented a dysregulated proteome, especially when looking at the phosphorylation level in cognitive-related categories (synaptic proteins, neuronal projection, neuron development, microtubule), and GTPases/kinase activity and chromatin related categories. Green tea, EE, and their phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function and phosphorylation, and autophagy to exert many of its beneficial biological actions Of interest for DS, it inhibits the activity of the Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A (DYRK1A), a DS candidate gene located in the 21q22.2 human chromosome region4,5. Previous work from our group showed that EGCG partially rescues the effects of overexpression of a DS candidate gene, DYRK1A, on the proteome and phosphoproteome of the hippocampus of TgDyrk1A mice6. However, the extent to which these mechanisms apply to a trisomy scenario is unknown. To get insight in these mechanisms we analyzed changes in protein abundances and phosphorylation in Ts65Dn mice, and their disomic counterparts in baseline conditions and upon three treatments known to improve cognition in Ts65Dn: i) green tea extract containing EGCG, ii) environmental enrichment (EE), and iii) their combination.
2020-10-13 | PXD018515 | Pride
Project description:Overexpression of the epidermal growth factor receptor family member Her-2/neu in breast cancer leads to autophosphorylation of the receptor, and induction of multiple downstream signaling pathways including Akt kinase to NF-ï«B cascade that is associated with poor prognosis. Previously, we demonstrated green tea polyhenol epigallocatechin 3-gallate (EGCG) inhibits growth of NF639 Her-2/neu-driven breast cancer cells via reducing receptor autophosphorylation, and downstream Akt and NF-ï«B activities (Pianetti et al., 2002). Interestingly, we noted that upon prolonged culture in the presence of EGCG some cells developed resistance to the polyphenol. Here we report that resistant cells have lost tyrosine phosphorylation on the Her-2/neu receptor. Surprisingly, they displayed elevated NF-ï«B activity, and inhibition of this activity sensitized cells to EGCG. Data from microarray analysis of the original and resistant NF639 populations of cells were subjected to Gene Set Enrichment Analysis (GSEA) pathway analysis, which revealed that the mitogen activated protein kinase (MAPK) pathway was activated in the resistant cells. Treatment of the resistant cells with a combination of EGCG and the MAPK inhibitor U0216 dramatically reduced colony growth and mesenchymal phenotype. Thus, activation of the MAPK pathway mediates resistance to EGCG. Our studies suggest that gene expression profiling of drug resistant cells may provide a mechanism of determining effective systemic therapies for treatment of these advanced cancers. Experiment Overall Design: Total RNA from original NF639 cells and EGCG resistant NF639 cells were harvested using the UltraspecII RNA isolation kit (Biotecx), following the manufacturerâs instruction. The RNA samples were submitted to Boston University Microarray Resource for microarray hybridization using Affymetrix Mouse 430A 2.0 chips. RNAs from two independent experiments were analyzed and data pooled for computational analysis.
2008-06-13 | E-GEOD-4140 | biostudies-arrayexpress
Project description:We have identified Epigallocatechin Gallate (EGCG) as a potent modulator of microglia function. Our aim was to determine whether EGCG affects the transcriptome of microglia and identify genes and gene sets that may underly the effects of EGCG on microglia function.
2024-07-17 | GSE208144 | GEO
Project description:Epigallocatechin-3-gallate (EGCG), a major active polyphenol of green tea, has been shown to downregulate inflammatory responses in macrophages; however, the underlying mechanism has not been understood. Recently, we identified the 67-kDa laminin receptor (67LR) as a cell-surface EGCG receptor that mediates the anti-cancer action of EGCG at physiologically relevant concentrations (0.1-1 mM). Here we show the molecular basis for the downregulation of TLR4 signal transduction by EGCG at 1 mM in macrophages. Anti-67LR antibody treatment or RNAi-mediated silencing of 67LR resulted in abrogation of the inhibitory action of EGCG on LPS-induced activation of downstream signaling pathways and target gene expressions. Additionally, we found that EGCG reduced the TLR4 expression through 67LR. Interestingly, EGCG induced a rapid upregulation of Tollip protein, a negative regulator of TLR-signaling, and this EGCG action was prevented by 67LR silencing or anti-67LR antibody treatment. RNAi-mediated silencing of Tollip impaired the TLR4 signaling inhibitory activity of EGCG. Taken together, these findings demonstrate that 67LR plays a critical role in mediating anti-inflammatory action of a physiologically relevant EGCG and Tollip expression could be modulated through 67LR. These results provide a new insight into the understanding of negative regulatory mechanisms for TLR4 signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases. We quantified expression profile of 210 inflammatory-relating genes in the 67LR-downregulated cells treated with LPS or/and EGCG by microarray
2010-04-20 | E-GEOD-21320 | biostudies-arrayexpress
Project description:We reported the molecular mechanisms of low combination doses of epigallocatechin-3-gallate and hydroxychavicol (EGCG+HC) in glioma cell lines 1321N1 and LN18. Using high throughput RNA sequencing, combined EGCG+HC exerted its anticancer effect by downregulating the axon guidance process and metabolic pathways, while simultaneously interfering with endoplasmic reticulum unfolded protein response pathway. Furthermore, EGCG+HC exerted its apoptotic effect through the alteration of mitochondrial genes such as MT-CO3 and MT-RNR2 in 1321N1 and LN18 cells respectively. EGCG+HC dynamically altered DYNLL1 alternative splicing expression in 1321N1 and DLD splicing expression in LN18 cell lines.
2022-04-13 | GSE193838 | GEO
Project description:EGCG, as an active oxygen scavenger, has a significant effect on inhibiting the greasiness of apples. However, the impact of greasiness on fruit storage and how EGCG eliminates this effect, as well as its influence on apple quality formation, have not been clarified. In this study, we found that exogenous application of EGCG effectively improved a series of nutritional growth indicators, including seedling growth status and photosynthetic activity. Additionally, it significantly increased indicators of reproductive growth, such as fruit diameter, soluble solids content, surface wax, and surface smoothness. Through our experiments, we further discovered that greasiness primarily affects fruit respiration, accelerating fruit decay and causing harm during storage, while EGCG mitigates this process. We also found that the application of tea residue had similar effects to exogenous EGCG. Collectively, these studies suggest that EGCG could be used as a novel foliar fertilizer to enhance overall fruit quality. Moreover, the application of tea residue has similar effects to EGCG, providing a cost-effective solution for apple production.
2023-12-02 | GSE248662 | GEO
Project description:Overexpression of the epidermal growth factor receptor family member Her-2/neu in breast cancer leads to autophosphorylation of the receptor, and induction of multiple downstream signaling pathways including Akt kinase to NF-kappaB cascade that is associated with poor prognosis. Previously, we demonstrated green tea polyhenol epigallocatechin 3-gallate (EGCG) inhibits growth of NF639 Her-2/neu-driven breast cancer cells via reducing receptor autophosphorylation, and downstream Akt and NF-kappaB activities (Pianetti et al., 2002). Interestingly, we noted that upon prolonged culture in the presence of EGCG some cells developed resistance to the polyphenol. Here we report that resistant cells have lost tyrosine phosphorylation on the Her-2/neu receptor. Surprisingly, they displayed elevated NF-kappaB activity, and inhibition of this activity sensitized cells to EGCG. Data from microarray analysis of the original and resistant NF639 populations of cells were subjected to Gene Set Enrichment Analysis (GSEA) pathway analysis, which revealed that the mitogen activated protein kinase (MAPK) pathway was activated in the resistant cells. Treatment of the resistant cells with a combination of EGCG and the MAPK inhibitor U0216 dramatically reduced colony growth and mesenchymal phenotype. Thus, activation of the MAPK pathway mediates resistance to EGCG. Our studies suggest that gene expression profiling of drug resistant cells may provide a mechanism of determining effective systemic therapies for treatment of these advanced cancers. Keywords: Drug resistance
2006-06-01 | GSE4140 | GEO