MPTAC determines APP fragmentation via sensing sulfur amino acid catabolism
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA453384 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7060341.fastq.gz | Fastqsanger.gz | |||
| SRR7060342.fastq.gz | Fastqsanger.gz | |||
| SRR7060343.fastq.gz | Fastqsanger.gz | |||
| SRR7060344.fastq.gz | Fastqsanger.gz | |||
| SRR7060345.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:The data from the analysis of transcripts of metabolic enzymes suggested the metabolic pathways that are directly/indirectly regulated by MPTAC. The transcript data also supports the metabolomics data, which suggested the connection of metabolic pathways regulated by MPTAC. The analysis of junction reads led to the discovery of involvement of MPTAC in splicing regulation.
2018-08-07 | GSE113609 | GEO
Project description:Impaired branched-chain amino acid (BCAA) catabolism has recently been implicated in the development of mechanical pain, but the underlying molecular mechanisms are unclear. Here we report that defective BCAA catabolism in dorsal root ganglion (DRG) neurons sensitizes mice to mechanical pain by increasing lactate production and expression of the mechanotransduction channel Piezo2. In high-fat diet-fed obese mice, we observe downregulation of PP2Cm, a key regulator of the BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm in DRG neurons exhibit mechanical allodynia under normal or SNI-induced neuropathic injury conditions. Furthermore, the VAS scores in the plasma of patients with peripheral neuropathic pain are positively correlated with BCAA contents. Mechanistically, defective BCAA catabolism in DRG neurons promotes lactate production through glycolysis, which increases H3K18la modification and drives Piezo2 expression. Inhibition of lactate production or Piezo2 silencing attenuates the pain phenotype of knockout mice in response to mechanical stimuli. Therefore, our study demonstrates a causal role of defective BCAA catabolism in mechanical pain by enhancing metabolite-mediated epigenetic regulation.
2023-08-27 | GSE235230 | GEO
Project description:Although gut microbiomes are generally symbiotic or commensal, some of microbiomes become pathogenic under certain circumstances, which is one of key processes of pathogenesis. However, the factors involved in these complex gut-microbe interactions are largely unknown. Here we show that bacterial nucleoside catabolism using gut luminal uridine is required to boost inter-bacterial communications and gut pathogenesis in Drosophila. We found that uridine-derived uracil is required for DUOX-dependent ROS generation on the host side, whereas uridine-derived ribose induces quorum sensing and virulence gene expression on the bacterial side. Importantly, genetic ablation of bacterial nucleoside catabolism is sufficient to block the commensal-to-pathogen transition in vivo. Furthermore, we found that major commensal bacteria lack functional nucleoside catabolism, which is required to achieve gut-microbe symbiosis. The discovery of a novel role of bacterial nucleoside catabolism will greatly help to better understand the molecular mechanism of the commensal-to-pathogen transition in different contexts of host-microbe interactions.
2020-04-07 | GSE140194 | GEO
Project description:Development, growth and adult survival are coordinated with available metabolic resources. The insulin/IGF and TOR signaling pathways relay nutritional status, thereby ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is down-regulated with age. This miRNA controls branched-chain amino acid (BCAA) catabolism and the activity of the TOR kinase, a central growth regulator. Metabolite analysis suggests that the mechanistic basis may be an accumulation of BCKAs, rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g. translational fidelity. Constitutive miR-277 expression as well as transgenic inhibition with a miRNA sponge construct shortens lifespan. Furthermore, constitutive miR-277 expression is synthetically lethal with reduced insulin signaling. Thus, optimal metabolic adaptation requires tuning of cellular BCAA catabolism by miR-277 to be concordant with systemic growth signaling.
2015-01-19 | GSE42442 | GEO
Project description:Heart Rate Fragmentation in WBS
| PRJNA1037272 | ENA
Project description:APP misexpression plays a crucial role in triggering a complex pathological cascade, leading to Alzheimer’s disease (AD). The aim of this study is for determine the influence of APP ectopic expression on the miRNA profiles of neuronal exosomes. In study, miRNA sequencing was done using the exosomes derived from N2A (control) and APP-N2A (N2A with APP overexpression).
2022-03-30 | E-MTAB-11106 | biostudies-arrayexpress
Project description:Lysosomal failure underlies pathogenesis of numerous congenital neurodegenerative disorders and is an early and progressive feature of Alzheimer’s disease (AD) pathogenesis. Here, we report that lysosomal dysfunction in Down Syndrome (Trisomy 21) requires the extra gene copy of amyloid precursor protein (APP) and is mediated by the beta cleaved carboxy terminal fragment of APP (APP-βCTF, C99). In primary fibroblasts from individuals with Down Syndrome (DS), lysosomal degradation of autophagic and endocytic substrates is selectively impaired causing them to accumulate in enlarged autolysosomes/lysosomes. Direct measurements of lysosomal pH uncovered a significant elevation (0.6 units) associated with slowed LC3 turnover and the inactivation of cathepsin D (CTSD) and other lysosomal hydrolases known to be unstable or less active when lysosomal pH is persistently elevated. RNA sequencing analysis excluded a transcriptional contribution to hydrolase declines. Normalizing lysosome pH by delivering acidic nanoparticles to lysosomes ameliorated lysosomal deficits, implicating pH elevation as their primary basis. Cortical neurons cultured from the Ts2 mouse model of DS exhibited lysosomal deficits similar to those in DS cells. Lowering APP expression with siRNA or BACE1 inhibition reversed cathepsin deficits in both fibroblasts and neurons. Deleting one BACE1 allele from adult Ts2 mice had similar rescue effects in vivo. The modest elevation of endogenous APP-βCTF needed to disrupt lysosomal function in DS is relevant to sporadic AD where APP-βCTF, but not APP, is also elevated. Our results extend evidence that impaired lysosomal acidification drives progressive lysosomal failure in multiple forms of AD.
2019-05-30 | GSE127880 | GEO
Project description:Bulk RNA-sequencing of astrocytes in the APP NL-F and APP PS1 models of ß-amyloidopathy, in which aspects of AD-related pathology progress at different speed, shows age-dependent gene expression changes. However, bulk RNA-seq does not provide insight into the heterogeneity of expression within this cell type, particularly relevant for such models, where reactive astrogliosis is most prominent in the vicinity of plaques. To investigate astrocyte heterogeneity in ß-amyloidopathy models, we thus performed single cell RNA-sequencing on astrocytes separated by FACS.
2024-03-21 | E-MTAB-13937 | biostudies-arrayexpress
Project description:Gene expression analysis of 2-month-old APP/APLP2 double-conditional Knockout (N-dCKO) mice and littermate APLP2 knockout controls, APP knockout and wildtype controls. Mouse hippocampus were dissected for RNA extraction and hybridization on Affymetrix microarrays.
2013-07-10 | E-GEOD-48622 | biostudies-arrayexpress
Project description:γδ T cells are lymphocytes that function in both innate and adaptive immune responses, and our laboratory has previously reported that both bovine and human γδ T cells are primed for secondary responses by tannin components of the unripe apple peel (APP). In this report we began to investigate the mechanism by which priming occurs. We performed a microarray analysis on sorted bovine γδ T cells treated with APP and observed significant increases in transcripts encoding select inflammatory cytokines, such as GM-CSF, IL-8, and IL-17, but not markers of TCR stimulation such as IFNγ. When injected into the gut of mice, APP induced a robust influx of neutrophils into both the blood and peritoneum as measured by FACS. Importantly, both GM-CSF and IL-8 proteins were detected in these animals. Further studies were performed using the human γδ T cell-line MOLT-14, as large numbers of cells were required for subsequent experiments. Using these cells we found that both the GM-CSF and IL-8 mRNAs were significantly upregulated and stabilized in cells treated with APP. Finally, we show that the ERK1/2 MAPK pathway was activated in APP-treated MOLT-14 cells, and that this pathway plays a role in the mRNA stabilization we observed. Together, our data describe a unique inflammatory response in bovine, murine, and human γδ T cells in response to APP, and suggest that mRNA stability mechanisms could account for the priming phenotype we previously observed.APP has a distinctive gamma delta T cells specific priming activity. Keywords: comparison of 2 treatment types, tannin, gamma delta T cells To begin to understand the effects of APP in innate immunity, we investigated the global gene expression profiles of stimulated bovine gamma delta T cells. Peripheral blood from 2 neonatal bovine calves was collected. gamma delta T cells were sorted to >97% purity using a FACS Vantage. Cells were placed in culture and stimulated with either an aqueous extract of APP (42.2ug/ml) or PBS for 4 hours after which RNA was extracted and processed for microarray analysis following standard protocols from Affymetrix.
2010-08-10 | E-GEOD-13321 | biostudies-arrayexpress