Ivermectin-exposed C.elegans (N2) transcriptomics
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PROVIDER: PRJEB59331 | ENA |
REPOSITORIES: ENA
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Project description:Ivermectin-exposed C.elegans (N2) transcriptomics
| PRJEB70616 | ENA
Project description:We have investigated the transcriptomic response of the model nematode Caenorhabditis elegans to ivermectin (IVM); an important anthelmintic for human and animal parasite control. The transcriptomic response of the mutant strain DA1316 avr-14(ad1302); avr-15(ad1250); glc-1(pk54), which is highly resistant to ivermectin due to null mutations in three glutamate-gated chloride channel subunits, was examined. Despite the resistant nature of this strain, pharyngeal pumping rate was decreased following 4 hrs exposure to 100ng/ml and 1μg/ml ivermectin resulting in significant change in the expression level of genes associated with a fasting response.
2011-04-01 | GSE22660 | GEO
Project description:We have investigated the transcriptomic response of the model nematode Caenorhabditis elegans to ivermectin (IVM); an important anthelmintic for human and animal parasite control. The transcriptomic response of the mutant strain DA1316 avr-14(ad1302); avr-15(ad1250); glc-1(pk54), which is highly resistant to ivermectin due to null mutations in three glutamate-gated chloride channel subunits, was examined. Despite the resistant nature of this strain, pharyngeal pumping rate was decreased following 4 hrs exposure to 100ng/ml and 1?g/ml ivermectin resulting in significant change in the expression level of genes associated with a fasting response. Matched cultures of synchronised C. elegans were grown to L4 stage on standard NGM plates with an OP50 bacterial lawn. The nematodes were then transferred to NGM plates containing 100ng/ml ivermectin, 1?g/ml ivermectin, or DMSO excipient only (control) for 4 hours. RNA was extracted from five biological replicates including controls for both the 100ng/ml ivermectin and 1?g/ml ivermectin experiments and hybridised to Affymetrix arrays.
2011-04-01 | E-GEOD-22660 | biostudies-arrayexpress
Project description:Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure
| PRJEB70467 | ENA
Project description:Here, we show that ivermectin suppress prostate cancer progression by inhibiting AR signaling pathway and attenuate cellular DNA damage repair capacity. We applied an integrated omics profiling including RNA-seq and Thermal proteome, that found pioneer factor Forkhead Box Protein A1 (FOXA1) and Non-homologous End Joining (NHEJ) repair executer Ku70/Ku80 was the direct target of Ivermectin in prostate cancer. Ivermectin binds to these two proteins and block their biological function, which results in blockade of AR signaling transcription and deficiency of DNA double-strand breaks (DSBs) repair system, and thereby leads to G0/G1 arrest and trigger synthetic lethality Our findings demonstrate both the effect and target of Ivermectin in prostate cancer comprehensively and systemically, indicating that use of Ivermectin may constitute a new therapeutic approach for prostate cancer.
2022-04-01 | GSE169356 | GEO
Project description:Rhipicephalus microplus is among the critical tick parasite of cattle farming globally. However, the massive use of ivermectin last decades induced the generation of the tick-resistant population. Unfortunately, despite extensive research the mode of action of ivermectin remains unclear. Due to the limited molecular information related to the resistance of R. microplus to ivermectin, we carried out a midgut comparative proteomics study between susceptible and resistant tick. Our tissues specificity approach also included tandem mass tags (TMT) couple to synchronous precursor selection (SPS)-MS3. Our proteomics scrutiny exhibits key biological process associated with blood digestion and anticoagulation in midgut. In addition, we could observe the significant shutdown of the translation mechanism in susceptible thinks. At the same time, resistant thick exhibited the over-accumulation of cytochrome P450, glutathione-S-transferase, and ABC transporters. A similar trend was observed in proteins like glutathione peroxides glutaredoxin, sulfiredoxin, and disulfide-isomerase, which suggest a possible activation of the oxidative metabolism as a potential strategy to cope with ivermectin treatment.
2024-01-29 | PXD031231 | Pride
Project description:Parasitic nematodes pose a significant threat to human and animal health, as well as cause economic losses in the agricultural sector. The use of anthelmintic drugs, such as Ivermectin (IVM), to control these parasites has led to widespread drug resistance. Identifying genetic markers of resistance in parasitic nematodes can be challenging, but the free-living nematode Caenorhabditis elegans provides a suitable model. In this study, we aimed to analyze the transcriptomes of adult C. elegans worms of the N2 strain exposed to the anthelmintic drug Ivermectin (IVM), and compare them to those of the resistant strain DA1316 and the recently identified Abamectin Quantitative Trait Loci (QTL) on chromosome V. We exposed pools of 300 adult N2 worms to IVM (10-7 and 10-8 M) for 4 hours at 20°C, extracted total RNA and sequenced it on the Illumina NovaSeq6000 platform. Differentially expressed genes (DEGs) were determined using an in-house pipeline. The DEGs were compared to genes from a previous microarray study on IVM-resistant C. elegans and Abamectin-QTL. Our results revealed 615 DEGs (183 up-regulated and 432 down-regulated genes) from diverse gene families in the N2 C. elegans strain. Of these DEGs, 31 overlapped with genes from IVM-exposed adult worms of the DA1316 strain. We identified 19 genes, including the folate transporter (folt-2) and the transmembrane transporter (T22F3.11), which exhibited an opposite expression in N2 and the DA1316 strain and were deemed potential candidates. Additionally, we compiled a list of potential candidates for further research including T-type calcium channel (cca-1), potassium chloride cotransporter (kcc-2), as well as other genes such as glutamate-gated channel (glc-1) that mapped to the Abamectin-QTL.
| S-EPMC10159168 | biostudies-literature
Project description:OCI AML2 cells were treated with the anti-parasitic ivermectin (single dose, two time points) in order to assess gene expression changes.
2010-01-06 | E-MEXP-2528 | biostudies-arrayexpress
Project description:The aim of this mRNA expression profiling experiment was to screen for ecotoxicogenomic fingerprints in zebrafish (Danio rerio) embryos as aquatic vertebrate non-target model exposed to sub lethal concentrations of Abamectin (CAS 71751-41-2). Abamectin is a heavily used insecticide applied for crop protection against sucking insects (i.e. Acari). The Insecticide Resistance Action Committee (IRAC) classified Abamectin after its mode of action (MoA) in the target organism as a Glutamate-gated chloride channel (GluCl) allosteric modulator (Group 6). In vertebrates, GluCl do not exist, but they are closely related to vertebrate glycine receptors (Wolstenholme 2012). The goal is to identify toxicogenomic profiles with predictive character and potential molecular key events (KE) explaining upstream adverse effects in aquatic non-target organisms. This will provide useful information to refine and improve existing adverse outcome pathways (AOP). Furthermore, integrating the obtained profiles for this and other tested chemicals in a collective database will enable us in the future to derive predictions about the ecotoxicological hazard for chemcials with unknown apical effects, based on similarly altered transcriptomic and proteomic profiles. In a modified version of the zebrafish embryo toxicity test (OECD 236), 15 fertilized eggs were exposed to two different sub lethal concentrations of Abamectin for 96 hours under semi-static conditions. Each test comprised of a low exposure (LE, 0.11 mg/L), mid exposure (ME, 0.22 mg/L), high exposure (HE, 0.44 mg/L) and negative control (NC) group and was performed in triplicates. At 96 hours post fertilization (hpf), 10 larvae were randomly picked for each sample and pooled for RNA and protein extraction with NucleoSpin RNA/Protein kit (Macherey-Nagel). RNA quality was assessed with a 2100 Bioanalyzer system (Agilent) before coding RNA was purified (PolyA selection with TruSeq RNA Library Prep Kit v2) and sequenced on an Illumina HiSeq 4000 System (Illumina) in 50 bp single read mode, producing roughly 30 million reads per sample. Adapter sequences were removed with trimmomatic and sequences were aligned to the D.rerio reference genome GRCz11 with STAR. Counting of feature mapped reads was performed through featureCounts. Library gene count tables were then merged to a single count matrix as input for differential gene expression analysis with DESeq2.
2021-10-15 | E-MTAB-9852 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include “maternal sterile”, “embryonic lethal”, “larval arrest”, “larval lethal”, “reduced brood size” and “egg shape variable”. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.
2016-07-27 | GSE75340 | GEO