Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360136 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We report the transcriptome and miRNAome of human embryonic kidney 293 cells upon the administration of ochratoxin A (OTA) and citrinin (CTN), to compare the individual and combined toxicity of these two mycotoxins. We identified largely differentially expressed miRNAs and corresponding genes, and the correlations between miRNAs and their target genes associated with apoptotic signaling were furthermore analyzed by pmi-RB-REPORT luciferase assay system. We concluded that hsa-miR-1-3p plays an essential role in promoting OTA and CTN-induced renal cytotoxicity.
2017-12-31 | GSE93148 | GEO
Project description:Ochratoxin A (OTA) is one of the most abundant mycotoxin contaminants in food stuffs and possesses carcinogenic, nephrotoxic, teratogenic and immunotoxic properties. Especially, severe nephrotoxicity is of great concern, as characterized by degeneration of epithelial cells of the proximal tubules and interstitial fibrosis. However, its mechanism of toxicity, hazard identification as well as genetic risk factors contributing to OTA toxicity in humans has been elusive due to the lack of adequate models that fully recapitulate kidney function in vitro. The present study attempts to evaluate dose-response relationships, identify the contribution of active transport proteins that govern renal disposition of OTA, and determine the role of metabolism in bioactivation and detoxification of OTA using a 3D human kidney proximal tubule microphysiological system (kidney MPS). We demonstrated that IC50 values of OTA in kidney MPS culture (0.375 – 1.21 µM) were in good agreement with clinical toxic concentrations of OTA in urine. Surprisingly, no enhancement of kidney injury biomarkers was evident in the effluents of kidney MPS after OTA exposure despite significant toxicity observed by LIVE/DEAD staining, rather these biomarkers were decreased in OTA concentration-dependent manner. Furthermore, the effect of 1-aminobenzotriazole (ABT) and 6-(NBD-4-ylthio-) hexanol (NBDHEX), pan-inhibitor of P450 and GST enzymes, respectively, on the OTA-induced toxicity in kidney MPS was examined, which resulted in significant enhancement of OTA-induced toxicity by NBDHEX (3 µM) treatment whereas ABT (1 mM) treatment decreased OTA-induced toxicity, suggesting the roles of GSTs and P450 enzymes in the detoxification and bioactivation of OTA, respectively. Additionally, OTA transport studies using kidney MPS in the presence and absence of inhibitor of organic anion transporter(s), probenecid (1 mM), revealed the role of organic anionic membrane transporter(s) in the kidney specific disposition of OTA. Our findings provide a better understanding of the mechanism of OTA-induced kidney injury which may support changes in risk assessment, regulatory agency policies on allowable exposure levels and determination of genetic factors in high-risk populations against OTA nephrotoxicity.
2020-10-22 | GSE151776 | GEO
Project description:The aim of this study was to reveal the genomic response of yeast cells to the related mycotoxins citrinin (CIT) and ochratoxin A (OTA). Both mycotoxins can be produced by the same filamentous fungi and co-contaminate the same foodstuff. However, it is not known whether CIT and OTA share the same toxicity mechanisms or not. We performed transcriptomic profiling experiments using microarray hybridization of a pdr5 mutant strain exposed separately to CIT or OTA and exposed to a combination of both toxins. A yeast pdr5 mutant was used, because it is significantly sensitized to both toxins. We find that CIT and OTA cause the rapid activation of largely non-overlapping gene sets. The most prominent functional group of CIT-activated genes corresponds to the cellular response to oxidative stress, while OTA-activated genes belong predominantly to single organism developmental processes and meiosis/sporulation. The combined exposure of CIT and OTA revealed a mixed response of functional gene groups. Our results demonstrate that CIT and OTA have distinguishable and independent biological effects with oxidative stress being a hallmark for CIT toxicity and the deregulation of developmental genes being the principal feature for OTA toxicity.
2016-10-01 | GSE84187 | GEO
Project description:The objective of this study is to analyze miRNA profiling in the kidneys of rats gavaged with OTA. To profile miRNAs in the kidneys of rats with OTA nephrotoxicity, high-throughput sequencing and bioinformatics approaches were applied to analyze the miRNAs in the kidney of rats following OTA treatment
2014-06-01 | E-MTAB-2475 | biostudies-arrayexpress
Project description:Mass spectrometric analyses of N- and O-glycosylation on human programmed cell death protein 1 extracellular domain (hPD-1 ECD) that expressed by human embryonic kidney 293 (HEK 293) and Chinese hamster ovary (CHO) cells
2024-01-11 | PXD048448 | iProX
Project description:Transcriptional profiling of human embryonic kidney 293 cells comparing transfected control pEGFP-C1 (empty vector) with pEGFP (survivin vector).
2014-10-21 | GSE43817 | GEO
Project description:Mycotoxin citrinin (CTN) is a secondary metabolite of fungi, becoming a contaminant widely found in foods, feeds, and fermented health supplements. CTN is known to disrupt microtubule and chromosome arrangement at high dose (50 - 150 μM), but the toxicological effect of CTN long-term exposure has not been clearly studied. To investigate the molecular mechanisms of genotoxic, clastogenic, and carcinogenic effects of CTN, RNA-seq was performed on HEK293 cells exposed to chronic 20 μM CTN treatment (3 days for short-term and 30 days for long-term). The transcriptomic profile may reveal some underlying mechanisms regarding chronic carcinogenic potential of CTN, providing information for risk assessment of CTN-contaminated grains and its commercial food products.
2023-03-01 | GSE218082 | GEO
Project description:Human embryonic kidney (HEK) cells 293 are analyzed by two state-of-the-art MS instruments (Thermo Orbitrap Fusion and Q Exactive HF) in quadruplicate for precision evaluation.
2018-05-08 | PXD009720 | iProX
Project description:Toxic effects of BDE209 in human embryonic kidney 293 cells (HEK 293)
| PRJNA243130 | ENA
Project description:This model is from the article:
Competing G protein-coupled receptor kinases balance G protein and β-arrestin signaling
Heitzler D, Durand G, Gallay N, Rizk A, Ahn S, Kim J, Violin JD, Dupuy L, Gauthier C, Piketty V, Crépieux P, Poupon A, Clément F, Fages F, Lefkowitz RJ, Reiter E. Mol Syst Biol.
2012; 8: 590. 22735336
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Abstract:
Seven-transmembrane receptors (7TMRs) are involved in nearly all aspects of chemical communications and represent major drug targets. 7TMRs transmit their signals not only via heterotrimeric G proteins but also through β-arrestins, whose recruitment to the activated receptor is regulated by G protein-coupled receptor kinases (GRKs). In this paper, we combined experimental approaches with computational modeling to decipher the molecular mechanisms as well as the hidden dynamics governing extracellular signal-regulated kinase (ERK) activation by the angiotensin II type 1A receptor (AT(1A)R) in human embryonic kidney (HEK)293 cells. We built an abstracted ordinary differential equations (ODE)-based model that captured the available knowledge and experimental data. We inferred the unknown parameters by simultaneously fitting experimental data generated in both control and perturbed conditions. We demonstrate that, in addition to its well-established function in the desensitization of G-protein activation, GRK2 exerts a strong negative effect on β-arrestin-dependent signaling through its competition with GRK5 and 6 for receptor phosphorylation. Importantly, we experimentally confirmed the validity of this novel GRK2-dependent mechanism in both primary vascular smooth muscle cells naturally expressing the AT(1A)R, and HEK293 cells expressing other 7TMRs.
2019-11-04 | BIOMD0000000842 | BioModels