Infection and herbicide exposure implicate c-Abl kinase in α-synuclein serine 129 phosphorylation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE287574 | GEO | 2025/09/24
REPOSITORIES: GEO
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Project description:Coexpression of alpha-synuclein and p25alpha in an oligodendroglial cell line elicites a degenerative response that relies on aggregation and phosphorylation of alpha-synuclein at Ser129 We used microarray analysis to detail the changes in gene expression caused by alpha-synuclein aggregation followed by cellular degeneration Alpha-synuclein was coexpressed with p25alpha in an oligodendroglial cell line and mRNA was isolated at 8, 12, and 16 hrs after transfection. Gene expression was analyzed by two identical microarray set-ups
2013-10-28 | E-GEOD-51781 | biostudies-arrayexpress
Project description:Infection and herbicide exposure implicate c-Abl kinase in α-synuclein serine 129 phosphorylation
| PRJNA1213773 | ENA
Project description:To gain insight into the signaling pathway(s) required for ABL1/ABL2-kinase activity or effected by Ponatinib treatment, we evaluated the consequences of single or double inactivation of ABL1/ABL2 cells, or Ponatinib treated cells on the transcriptome of breast cancer cells. To examine the consequences of depleting the ABL kinases, or Ponatinib treatment on the transcriptome of lung metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 321 genes were significantly differently expressed in Ponatinib treated LM2 cells, and 73 genes were differently expressed in double inactivation of ABL1/ABL2 LM2 cells. However, only about 3.4 percent of Ponatinib affected genes can also be changed by ABL knocking down.
2018-03-01 | GSE95079 | GEO
Project description:Chronic infection of the human stomach with Helicobacter pylori leads to a variety of pathologic sequelae including peptic ulcer and gastric cancer, resulting in significant human morbidity and mortality. Several genes have been implicated in disease related to H. pylori infection including the vacuolating cytotoxin and the cag pathogenicity island. Other factors important for establishment and maintenance of infection include urease enzyme production, motility, iron uptake and stress response. We utilized a C57BL/6 mouse infection model to query a collection of 2400 transposon mutants in two different bacterial strain backgrounds for H. pylori genetic loci contributing to colonization of the stomach. Microarray based tracking of transposon mutants allowed us to monitor the behavior of transposon insertions in 758 different gene loci. Of the loci measured 223 (29%) had a predicted colonization defect. These include previously described H. pylori virulence genes, genes implicated in virulence in other pathogenic bacteria and 81 hypothetical proteins. We have retested 10 previously uncharacterized candidate colonization gene loci by making independent null alleles and confirmed their colonization phenotype using competition experiments and determination of the dose required for 50% infection. Of the genetic loci retested, 60% have strain specific colonization defects while 40% had phenotypes in both strain backgrounds for infection, highlighting the profound effect of H. pylori strain variation on the pathogenic potential of this organism. This SuperSeries is composed of the SubSeries listed below.
2006-12-15 | GSE6531 | GEO
Project description:Helicobacter pylori is a widespread Gram-negative pathogen involved in a variety of gastrointestinal diseases, including gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Immune responses aimed at eradication of H. pylori often prove futile, and paradoxically play a crucial role in the degeneration of epithelial integrity and disease progression. We have previously shown that H. pylori infection of primary human monocytes increases their potential to respond to subsequent bacterial stimuli – a process that may be involved in the generation of exaggerated, yet ineffective immune responses directed against the pathogen. In this study, we show that H. pylori-induced monocyte priming is not a common feature of Gram-negative bacteria, as Acinetobacter lwoffii induces tolerance to subsequent Escherichia coli lipopolysaccharide (LPS) challenge. Although the increased reactivity of H. pylori-infected monocytes seems to be specific to H. pylori, it appears to be independent of its virulence factors Cag pathogenicity island (CagPAI), cytotoxin associated gene A (CagA), vacuolating toxin A (VacA) and g-glutamyl transferase (g-GT). Utilizing whole-cell proteomics complemented with biochemical signaling studies, we show that H. pylori infection of monocytes induces a unique proteomic signature compared to other pro-inflammatory priming stimuli, namely LPS and the pathobiont A. lwoffii. Contrary to these tolerance- inducing stimuli, H. pylori priming leads to accumulation of NF-кB proteins, including p65/RelA, and thus to the acquisition of a monocyte phenotype more responsive to subsequent LPS challenge. The plasticity of pro-inflammatory responses based on abundance and availability of intracellular signaling molecules may be a heretofore underappreciated form of regulating innate immune memory as well as a novel facet of the pathobiology induced by H. pylori
2023-11-10 | PXD045072 | Pride
Project description:Coexpression of alpha-synuclein and p25alpha in an oligodendroglial cell line elicites a degenerative response that relies on aggregation and phosphorylation of alpha-synuclein at Ser129 We used microarray analysis to detail the changes in gene expression caused by alpha-synuclein aggregation followed by cellular degeneration
2013-10-28 | GSE51781 | GEO
Project description:Aggregation of α-synuclein may trigger the development of synucleinopathies, a progressive neurodegenerative disease such as Parkinson's disease and Dementia with Lewy bodies. We demonstrate RNA initiates α-synuclein phase transition in vitro, however, RNA binding ability and its motif remain unclear. Here, we indicate purified human α-synuclein protein preferentially binds to guanine-rich RNA sequences by RNA Bind-N-Seq using a pool of random 24-mer RNA oligonucleotides in vitro. Importantly, these hit motifs were required consecutive guanines not random, suggesting that RNA G-quadruplexes binds to α-synuclein. We also confirmed that GC content and skew of α-synuclein-enriched RNA sequences were similar to that of BG4 (G-quadruplex antibody)-enriched RNA sequences. Taken together, these data suggest that α-synuclein binds to RNA-formed G-quadruplex.
2023-07-17 | GSE235418 | GEO
Project description:Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected. Factorial design comparing SNCA knock-out mice with wild type littermates in two different tissues (striatum, cerebellum) at two different timepoints (6 and 21 month)
2010-07-21 | E-GEOD-19534 | biostudies-arrayexpress
Project description:Background Gastric Helicobacter pylori colonization leads to iron deficiency anemia (IDA), especially in children and adolescents. However the pathogenesis is poorly understood. Objective We sought to identify specific H. pylori genes involved in IDA development, by comparing bacterial genome-wide expression profiling in patients affected or not. Methods H. pylori were isolated from four children with IDA and four from matched controls without IDA. Based on these isolates, cDNA microarrays under iron-replete or depleted conditions were systematically performed to compare gene expression profiles at the whole genome level. Real-time reverse-transcription (RT-) PCR and protein assays were performed for further assessing the profile differentiation of the identified H. pylori IDA-associated genes. Results We identified 29 and 11 genes with significantly higher or lower expression in the IDA isolates compared to non-IDA isolates, respectively. Especially notable were higher expression of sabA gene encoding sialic acid-binding adhesin in the IDA isolates, which was confirmed by real-time RT-PCR study. Moreover, iron-depletion in vitro led to up-regulation of fecA1 and frpB1 genes and down-regulation of pfr, as predicted. Known iron-regulated genes such as fur, pfr, fecA, and feoB did not significantly differ between both groups. The IDA isolates had significantly higher expression of vacuolating cytotoxin gene vacA than non-IDA isolates, consistent with the results of VacA protein assays. There were no significant differences in bacterial growth value between IDA and non-IDA isolates. Conclusions It is likely that H. pylori carrying high expression of sabA causes IDA, especially in children and adolescents who have increased daily iron demand. In addition, it is possible that several host-interactive genes, including vacA, may play a synergistic role for sabA in IDA development.
2017-07-25 | GSE101807 | GEO
Project description:Parkinson's disease is a prevalent neurodegenerative disorder for which there is no cure. The cause of PD symptoms is loss of dopamine neurons in the midbrain, but it is not known why these neurons die. Pesticide exposure is epidemiologically associated with PD, and administration of the organic pesticide rotenone to rats recapitulates most of the behavioral, neurochemical, and neuropathological findings in PD, including specific death of dopamine neurons. We have developed an in vitro model of rotenone toxicity using a dopaminergic cell line (SK-N-MC neuroblastoma cells) that mimics many of the cellular changes seen with in vivo rotenone toxicity and with PD, such as alpha-synuclein aggregation and oxidative damage. We are currently using this simple model to explore mechanisms of dopaminergic neurodegeneration, with our ultimate goal being the discovery of novel mechanisms for dopaminergic neuroprotection in PD. We will examine gene expression profiles of cultured SK-N-MC cells at several time points during rotenone exposure to determine pathways involved in rotenone toxicity and dopaminergic degeneration. We will compare these profiles to baseline profiles of rodent dopaminergic neurons that we have already obtained, as well as to profiles of dopamine neurons from rotenone-treated rats that we will obtain in the near future. We will also compare these data to published results from SN neurons from human PD patients. This technique will not only help us to detect gene expression changes relevant to dopaminergic neurodegeneration in PD, but it will allow us to determine if the SK-N-MC system can be reliably used to screen for neuroprotective therapies for PD. We anticipate that SK-N-MC cells will show a relevant subset of the gene changes seen in dopamine neurons in vivo and that this will guide us in the sorts of mechanisms and drugs that can be screened in this system. Chronic exposure to low levels of rotenone causes changes in gene expression in SK-N-MC cells that sensitize the cells to toxic insults. We also hypothesize that there are several compensatory protective pathways that are stimulated by chronic rotenone, although these pathways are ultimately ineffective at preventing damage. We anticipate that gene expression profiling of rotenone-treated cells over time will suggest several novel strategies for neuroprotective intervention. SK-N-MC cells will be grown in three different media: media only, vehicle (EtOH), and rotenone (5 nM). All current experimental evidence in our lab indicates that vehicle-treated cells are indistinguishable from media-only cells. Rotenone-treated cellls have a stereotypical response in culture. At one week, the only noticed change is an increase in alph-synuclein aggregation. At two weeks, evidence of increased oxidative stress appears (increased protein carbonyls and lipid peroxidation). At four weeks, the cells are markedly sensitized to oxidative challenge with H2O2. Therefore, we will examine gene expression at baseline, and during 1, 2, and 4 weeks of rotenone treatment. Three experiments will be performed, each lasting 4 weeks. For each experiment, three separate dishes of vehicle-treated, and rotenone-treated cells will be harvested at 1, 2, and 4 weeks (18 independent samples). Untreated, media-only cells will be harvested after 1 week in vitro to serve as baseline cells. Total RNA will be isolated. An equal amount of RNA from one dish per experiment per group will be used to compose the final samples. Therefore, each independent sample will consist of RNA from 3 separate experiments. This will allow us to take advantage of a pooling strategy, yet not sacrifice technical and biological replication. 21 samples will be sent to the Consortium. Three will be from untreated cells. Nine will be vehicle-treated at 1, 2, and 4 weeks (3 each). Nine will be rotenone-treated at 1, 2 , and 4 weeks (3 each). Each sample will be labeled and hybridized to one Affymetrix Human Genome U133 Plus 2.0 Gene Chip. With assistance of the consortium, we will analyze the data using the Signifiance Analysis of Microarrays (SAM) program and self-organizing map algorithms.
2009-09-23 | E-GEOD-4773 | biostudies-arrayexpress