Mapping of Oxidative Damage to RNA by Hypochlorous Acid
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB73991 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12757400.fastq.gz | Fastqsanger.gz | |||
| ERR12757401.fastq.gz | Fastqsanger.gz | |||
| ERR12757402.fastq.gz | Fastqsanger.gz | |||
| ERR12757403.fastq.gz | Fastqsanger.gz | |||
| ERR12757404.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:RNA oxidation HOCl Complement
| PRJEB84071 | ENA
Project description:Hypochlorous acid (HOCl) is a potent oxidant that is produced endogenously in mammalian tissue by phagocytes. Exogenous exposure to HOCl also can occur following inhalation of chlorine gas. HOCl has been implicated as a source of oxidative stress associated atherosclerosis and other diseases. The purpose of this study was to identify dose-dependent transitions in cellular response to hypochlorous acid (HOCl), with a focus on understanding how various cellular defense and stress dose-responses overlap.
2009-04-01 | GSE15457 | GEO
Project description:Purpose: The aim of this study was to determine the transcriptional response of P. aeruginosa PA14 to HOCl and HOSCN stress, and determine genes dependent on RclR (PA14_07340) regulation. Methods: PA14 WT and ∆rclR exponential phase cultures were exposed to sub-lethal amounts of HOCl or HOSCN (2.2 or 0.8 mM, respectively), or untreated, and after 20 minutes of exposure, RNA was extracted and gene expression analysed by RNA-seq. Reads Per Kilobase per Million mapped reads (RPKM) were determined and the log2 fold change of the RPKM values of treated WT compared to untreated WT, or treated WT compared to treated ∆rclR was calculated. Genes with a log2 fold change of >1.5 were considered upregulated and genes with a log2 fold change of <-1.5 were considered downregulated. Results: In the WT strain, HOCl exposure resulted in upregulation of 231 genes and downregulation of 20 genes, and HOSCN exposure caused upregulation of 105 genes and downregulation of 16 genes. There was considerable overlap in the transcriptional response to HOCl and HOSCN, with 74 genes being induced in response to both oxidants. Genes upregulated by HOCl and HOSCN included those involved in sulphur and taurine transport, those encoding the type 3 secretion system, the MexEF-OprN drug efflux pump, and the putative peroxiredoxin RclX (PA14_07355). Comparison of the treated WT and treated ∆rclR strains revealed that in the presence of HOCl RclR upregulated 42 genes and downregulated 7 genes, and in the presence of HOSCN upregulated 132 genes and downregulated 213 genes. In the presence of both HOCl and HOSCN, RclR was required for upregulation of rclX as well as pyocyanin biosynthesis genes. In the presence of HOSCN, RclR downregulated a large number of genes, including those encoding chaperones. Conclusions: Our data have identified that the transcriptional response of P. aeruginosa to HOCl and HOSCN is multifaceted and appears to be linked to antibiotic resistance and the virulence factors pyocyanin and type 3 secretion. Determination of the regulon of the transcriptional regulator RclR after HOCl and HOSCN exposure suggests RclR has a role in coordinating the P. aeruginosa response to these oxidants.
2020-11-02 | GSE124385 | GEO
Project description:We evaluated the changes in the transcriptome of a melanoma cell line, B16F10, and spleen isolated murine T cells when in the presence of hypochlorous acid (HOCl) using RNA-sequencing technologies.
2020-12-30 | GSE164014 | GEO
Project description:Extracellular traps (NETs) are released by neutrophils during inflammation and play a role in pathology of diseases such as atherosclerosis, as well as their innate immune function of clearing infection. NETs are composed of a mesh of DNA and histones and contain various anti-microbial granule proteins, such as myeloperoxidase (MPO), which remains enzymatically active. This can result in the production of the reactive oxidant hypochlorous acid (HOCl), which reacts readily with proteins. However, whether histones and other NET-associated proteins contain HOCl-modified proteins is unknown. This is significant as recent studies show that exposure of histones to HOCl alters their extracellular reactivity to promote inflammatory signaling in vascular cells. In this study, we used a proteomic approach to characterise the protein composition of NETs and examine whether histones and other proteins contain oxidative protein-translational modifications resulting from reactions with HOCl. NETs were collected from neutrophil-like PLB-985 cells and primary neutrophils stimulated with phorbol myristate acetate (PMA) or nigericin, a bacterial peptide derived from Streptomyces hygroscopicus. Exposure of proteins to HOCl results in the formation of nitrile and aminoadipic semialdehyde formation on lysine residues, chlorination of tyrosine and tryptophan residues together with methionine oxidation products. Evidence was obtained for the presence of tyrosine chlorination on histones, particularly histone H4, and other proteins like quinone oxidoreductase. Other PTMs, including citrullination and acetylation were also detected on histones (H1, H2A, H3 and H4). Chlorination of the histone H4 peptide TVTAMDVVYALK(R) by HOCl was more abundant in NETs obtained from neutrophils exposed to PMA compared to nigericin, consistent with nigericin triggering NET release via a non-oxidative pathway. Current studies are investigating whether histone modifications occur before or after release from the cell. These findings provide the first evidence that HOCl induces histone modifications on NETs, which may be relevant in disease.
2025-05-30 | PXD060348 | Pride
Project description:Hypochlorous acid (HOCl) is a potent oxidant that is produced endogenously in mammalian tissue by phagocytes. Exogenous exposure to HOCl also can occur following inhalation of chlorine gas. HOCl has been implicated as a source of oxidative stress associated atherosclerosis and other diseases. The purpose of this study was to identify dose-dependent transitions in cellular response to hypochlorous acid (HOCl), with a focus on understanding how various cellular defense and stress dose-responses overlap. Experiment Overall Design: RAW 264.7 cells were grown to 80-90% confluency in DMEM supplemented with supplemented with 10% fetal bovine serum (FBS), 10 mM HEPES, 100 U penicillin/ml, and 100 µg streptomycin/ml. Cells were treated with 0, 0.14, 0.35, 0.7, 1.4, 2.1, 2.8 or 3.5 mM HOCl in medium for 6 hr. Total RNA was isolated from cells with TRIzol according to manufacturer's instructions and then subjected to cleanup using RNase-Free DNase Set and RNeasy Mini kit. The resultant DNA-free RNA was diluted in RNase-free H2O and quantified by Nanodrop at 260 nm. The quality of RNA samples was confirmed using RNA Nano Chips with Agilent 2100 Bioanalyzer. RNA samples were stored at â70 oC until use. Experiment Overall Design: From 5 micrograms of total RNA, cDNA was synthesized using a one-cycle cDNA synthesis kit (Affymetrix Corp., Santa Clara, CA). cDNA was transcribed to cRNA which was then biotin-labeled using GeneChip IVT labeling kit. Fifteen micrograms of labeled cRNA were then hybridized to an Affymetrix Mouse Genome 430 2.0 Array at 45°C for 16 hr. Biological cRNA replicates (n = 3) were each hybridized to an individual array. After being washed using the GeneChip Fluidics Station 450, arrays were scanned using a GeneChip 3000 scanner and intensity values were extracted from the CEL file using Array Assist software (Stratagene, La Jolla, CA). Experiment Overall Design:
2009-04-12 | E-GEOD-15457 | biostudies-arrayexpress
Project description:Examining the response of chemostat cultured, steady-state, Escherichia coli MG1655 to 10 mg/l hypochlorous acid (HOCl)
2005-12-01 | E-MEXP-244 | biostudies-arrayexpress
Project description:Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of pro-inflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes. The pathways for H2O2 and HOCl resistance in E. coli have been well-studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms. These results raise the intriguing possibility of developing treatments for inflammatory gut diseases that could sensitize pro-inflammatory enterobacteria to killing by the immune system while sparing anti-inflammatory, health-associated species.
2019-08-15 | GSE127961 | GEO
Project description:Epidermolysis bullosa (EB) is a group of rare inherited skin disorders characterized by mechanobullous skin fragility and painful wounds that are readily infected by bacteria, particularly Staphylococcus (S.) aureus. More effective approaches for decreasing wound colonization and infection by pathogenic bacteria are necessary to reduce EB morbidity and mortality. To assess the ability of a low pH, hypochlorous acid (HOCl)-based spray to reduce S. aureus burden, promote wound healing, and restore a healthier skin microbiome. Pilot 12-week open-label study of APR-TD011, a low pH (2.5-3) acid-oxidizing spray containing HOCl (0.0038%), on chronic wounds of EB patients. Patients used the spray daily for 8 weeks on designated wounds. Wounds were assessed clinically and swabbed for microbiome analysis using full-length 16S rRNA sequencing before, at Weeks 4 and 8 of treatment, and at 4 weeks post-treatment. Thirteen of 15 enrolled patients, most of whom had dystrophic EB, were culture-positive for S. aureus at baseline. Sequencing data showed S. aureus had the highest relative abundance (34%), followed by Acinetobacter guillouiae and Pseudomonas poae. S. aureus relative abundance was reduced by Weeks 4 (to 11%), 8 (primary endpoint; to 10%, p<0.01), and still at Week 12 (to 9.7%), including for methicillin-resistant S. aureus. Overall, bacterial diversity increased with treatment and wound sizes decreased, correlating with reduction in S. aureus (p=0.64). These findings suggest that acid-oxidizing HOCl sprays may be an effective adjunctive therapy to reduce bacterial dysbiosis and infection risk in EB wounds, while promoting wound healing.
2025-08-20 | GSE288051 | GEO
Project description:RNA-Seq analysis of melanoma cells, B16F10, in the presence of hypochlorous acid (HOCl)
| PRJNA688512 | ENA