Proteomics study of THP-1 monocytic cells exposed to surface modified-gold nanoparticles
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Monocyte
SUBMITTER: 
Jimmy Ytterberg
LAB HEAD: Roman A. Zubarev
PROVIDER: PXD010858 | Pride | 2019-03-18
REPOSITORIES: Pride
Dataset's files
Items per page: 5 1 - 5 of 108 |
Publications
Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study.
Gallud Audrey A Klöditz Katharina K Ytterberg Jimmy J Östberg Nataliya N Katayama Shintaro S Skoog Tiina T Gogvadze Vladimir V Chen Yu-Zen YZ Xue Ding D Moya Sergio S Ruiz Jaime J Astruc Didier D Zubarev Roman R Kere Juha J Fadeel Bengt B
Scientific reports 20190313 1
Systems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups, i.e., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxici ...[more]
Similar Datasets
Project description:Transcriptome comparison to assess the responses of human monocytic cells (THP-1) to gold-nanoparticles (Au-NPs) of two different diameter sizes (5 or 20 nm) with different surface functional groups, i.e., alkylammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated thiolate Au-NPs.
2019-06-04 | E-MTAB-7093 | biostudies-arrayexpress
Project description:Whole-genome expression microarray experiments were conducted to assess the response of C. metallidurans CH34 to aqueous Au(III)-chloride and identify possible biochemical pathways for Au detoxification. Four microarray experiments were conducted to assess gold response at low, medium and high Au(III)-chloride concentrations (i.e., 10, 50 and 100 µM Au(III)-chloride) and different induction times (10 and 30 minutes with 50 µM Au(III)-chloride). Based on these arrays, the differentially expressed genes upon gold-exposure can be identified. The four microarray experiments (10, 50 and 100 µM Au(III)-chloride at 10 minutes and 50 µM Au(III)-chloride at 30 minutes) were all performed in biological triplicate and containing three (in-slide) technical repeats. For all conditions, the metal-induced sample (Cy5) was compared with the non-induced sample (Cy5) to identify those genes that were differentially expressed upon gold exposure.
2010-06-20 | E-GEOD-14049 | biostudies-arrayexpress
Project description:Homogeneous gold nanoclusters (Au NCs) have been widely utilized in drug delivery, chemical sensing, bioassays and bio-labeling due to their unique physical and chemical properties. However, few attentions have been paid on their application in detecting protein post-translational modifications. Herein, we developed a homogeneous reaction system with water-soluble zwitterionic Au NCs to capture glycopeptides from the complex biological samples for the first time. The unique characteristics of Au NCs, such as the molecular-like property, the excellent homogeneity in aqueous solution and organic solvent responsive precipitation, the easy preparation in only 4.5 hours, contribute to the high efficiency and high through-put for capturing the targeted glycopeptides. Briefly, the Au NCs and tryptic protein samples were incubated together in a homogeneous aqueous solution and then the glycopeptides were collected by co-precipitation with zwitterionic Au NCs dur-ing gradually dropping addition of acetonitrile. Compared with the conventional heterogeneous system with solid-state ad-sorbents, the number of characterized glycosylation sites was improved 35%. Finally, the MS detection limitation as low as 50 amol was achieved for the tryptic digests of standard glycoprotein (IgG) and 1576 glycosylation sites from 713 glycopro-teins were feasibly identified from only 60 μg mouse liver proteins
2017-03-29 | PXD005635 | Pride
Project description:Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. All animal studies were carried out under approved IACUC protocols at the University of Washington.
2009-07-06 | E-GEOD-12140 | biostudies-arrayexpress
Project description:As a humanized mouse antibody, SM5-1 can target a membrane protein of about 230kDa over-expressed in hepatocellular carcinoma (HCC), melanoma and breast cancer and it has been found to inhibit the progress of tumor cells. In this study, SM5-1 conjugated gold nanoparticles were prepared to study the antitumor efficacy in the treatment of HCC-LM3-fLuc tumor. The results showed that AU-SM5-1 could inhibit HCC-LM3 hepatocellular carcinoma cell proliferation up to 71.26% at the concentration of 0.5mg/ml contrast with SM5-1 and gold nanoparticles. In order to address the mechanism of the antiproliferative effects of AU-SM5-1, we examined the gene expression in HCC-LM3-fLuc tumor cells based on gene-chip screening. The gene chip results showed that some cycle-related and reactive oxygen species (ROS) related genes including up-regulated P21 and down-regulated duox2 and nox1 genes which were validated by real-time quantitative polymerase chain reaction (PCR).
2014-07-11 | E-GEOD-59284 | biostudies-arrayexpress
Project description:Recombination-mediated linking of homologous chromosomes is a unique meiotic feature that enables the halving of chromosomal ploidy in sexual life cycles. Meiotic recombination is initiated by programmed DNA double-strand breaks (DSBs) that are generated by focal multi-protein clusters that condense onto chromosomal axes by poorly understood mechanisms. We discovered in mice that a DBF4-dependent kinase (DDK)–modulated interaction between IHO1 and the chromosomal axis component HORMAD1 effects the formation of axis-bound IHO1 platforms that enhance nucleation of cytologically distinguishable DSB-machinery clusters. This IHO1-HORMAD1-mediated seeding of the DSB-machinery ensures that sufficient DSBs form for efficient pairing of homologous chromosomes. In the absence of IHO1-HORMAD1 interaction, residual DSB activity depends on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, meiotic DSBs are ensured by complementing pathways that differentially effect seeding and growth of DSB-machinery clusters, and that synergistically enable assembly of the DSB machinery on chromosomal axes.
2024-02-23 | PXD042179 | Pride
Project description:We used Au nanoparticles (Au-NPs) as a model for studying particle specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, free living nematode Caenorhabditis elegans. Global genome expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC10 (5.9 mg L-1) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways associated with 38 of these genes were identified. Activation of 26 pqn/abu genes from noncanonical Unfolded Protein Response (UPR) pathway and up-regulation of molecular chaperones (hsp-16.1, hsp-70, hsp-3 and hsp-4) were observed and are likely indicative of endoplasmic reticulum stress. Inhibition of abu-11 with RNAi showed increase in mortality in Au-NP exposed nematodes suggesting possible involvement of abu-11 (a gene associated with specific to C. elegans UPR) in a protective mechanism against Au-NPs. Exposure to Au-NPs also caused activation of genes involved in apoptosis and necrosis and resulted ultimately in 10% mortality. These results demonstrate that Au-NPs are bioavailable and cause adverse effects to a model ecoreceptor which activate both general and specific biological pathways. Age-synchronized L3 nematodes (about 2000 nematodes per replicate with 3 replicates per treatment) were exposed to LC10 (5.9 mgL-1 ) of 4-nm citrate-coated Au-NP using 6 cm petri-dishes with 4 ml of exposure solution per dish. The N2 nematodes at L3 stageused were used and they were exposed in 50% K-Medium (31.68 mM KCl, 51.37 mM NaCl) for 12h. At 12 h all solutions were replaced with 50% K-Medium and left for another 12 h. After 24 h RNA was extracted from each of the replicates .
2012-04-15 | E-GEOD-32521 | biostudies-arrayexpress
Project description:Although immediate early genes (IEGs) such as Bdnf, Arc and Egr1, have been implicated in plasticity, the larger pathways related to memory and memory disorders are not well understood. Here, we combined statistical Affymetrix microarray and behavioral analyses to identify key genes and pathways associated with aging-related cognitive impairment. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal). ANOVA, linear contrasts, and overrepresentation analyses identified genes and pathways that differed from Y generally with aging (in both AU and AI) or selectively with cognitive status (only in AI or AU). Plasticity pathways, including insulin/cAMP/IEG signaling, and glycogenolytic and lipogenic pathways, were selectively downregulated (5 days) in AI, whereas Notch2 (regulating oligodendrocyte differentiation) and myelination pathways were upregulated (particularly at 21 days). Downregulation with general aging occurred in signal transduction and axonal growth/transport pathways, whereas upegulation occurred in immune/inflammatory, lipid metabolism/transport (e.g., Lxr-Srebf1), and lysosomal pathways. In AU, receptor/signal transduction genes were selectively upregulated, suggesting possible compensatory mechanisms. Immunohistochemistry confirmed and extended results to the protein level. Thus, this study identified novel cognition-linked processes, suggesting a new model in which energy-intensive, plasticity/lipogenic processes and energy-generating pathways necessary for learning are coordinately downregulated during training, while myelinogenic programs that impair cognition are concurrently activated. Experiment Overall Design: Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals (NT, 5D, and 21D, N=10/group). Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal)
2007-11-29 | E-GEOD-5666 | biostudies-arrayexpress
Project description:15N-labeled N-acetylglucosamine (NAG) fed to B. infantis cells are incorporated into its proteome. This indicates that NAG, an amino sugar residue of human milk oligosaccharides (HMO) and other biopolymers, is used as a nitrogen source. Transcriptomics while subsisting on NAG nitrogen are consistent with the proteomics results. This further indicates that B. infantis utilizes NAG nitrogen in and shunts it towards a fundamental cellular processes.
2023-05-18 | PXD035809 | Pride
Project description:Calpains are intracellular Ca2+-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis; however, their substrate specificity remains unclear because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains’ substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10’ of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. The kcat/Kms for 119 sites ranged from 12.5~1,710 M-1s-1. Most sites were cleaved by both calpain-1 and -2 with a similar kcat/Km. The aa compositions of the novel sites were not significantly different from the 420 previously reported sites, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is due to the substrates’ higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) than C-terminal (P’-sites) were preferred for proteolysis. Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achieved kcat/Km prediction with r=0.834, and binary-QSAR modeling attained 64.8% prediction accuracy for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3’, P4’, and P1-P2 contexts. This study increases our understanding of calpain substrate specificities, and opens calpains to “next-generation,” i.e., activity-related quantitative and context-dependent analyses.
2016-07-19 | PXD002532 | Pride