Alteration of MicroRNA Expression Profile Linked to Microcystin-LR-Induced Tumorigenicity in Human WRL-68 Cell Line
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Lizhi Xu
PROVIDER: E-GEOD-30560 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Microcystins (MCs) are cyclic hepatotoxins produced worldwide by various species of cyanobacteria. Their structure includes two variable amino acids (AAs) and most of the studies focused on the most toxic variant: the microcystin LR (MC-LR). However, more than 80 MC variants have been described to date. Despite ingestion being the major pathway of human exposure, few in vivo studies have demonstrated macroscopic effects on the gastro-intestinal tract, but no data are available on the affected pathways by several variants on intestinal cells. Here, using a non-selective method, we investigated for the first time the effect of MC-RR and MC-LR on the human intestinal cell line Caco-2 and compared their response at the pangenomic scale. The cells were incubated for 4 hrs or 24 hrs with the same range of sub-lethal concentrations of MC-RR or MC-LR. Low effects were observed for both variants after a short-term exposure. On the contrary, dose-dependent modulations of the genes transcription levels were noticed with MC-RR and MC-LR after 24 hrs. Furthermore, the genomic profiles induced by both variants were similar suggesting a common toxicity mechanism but with higher modulation following MC-LR than MC-RR exposure. However, the functional annotation revealed major differences between the variants effects. Indeed, the well-known MC-LR affected mainly two pathways, the oxidative stress response and the cell cycle regulation, which did not elicit significant alteration following MC-RR exposure. This work is the first comparative description of the MC-LR and MC-RR effects on a human intestinal cell model. It allowed us to suggest differences in the mechanism of toxicity for MC-RR and MC-LR. These results illustrate that the toxicity of MC variants remains a key point for risk assessment. Differentiated Caco-2 cells were exposed to microcystins in free FCS culture medium for either 4 or 24 hours. Sub-lethal concentrations of 10, 50 and 100 M-BM-5M of MC-LR or MC-RR were chosen for 4 hours, while 1, 5 and 10 M-BM-5M were selected for 24 hours. For each condition (including the controls), the solvent concentration was fixed to 2% EtOH for MC-LR and 1.5% of 80% MeOH for MC-RR. Four to five culture replicates per condition were done.
2012-12-31 | E-GEOD-29861 | biostudies-arrayexpress
Project description:Zebrafish (Danio rerio) were obtained from the Zebrafish Research Facility maintained in the Center for Environmental Biotechnology at the University of Tennessee. Fish husbandry, spawning, and experimental procedures were conducted with approval from the University of Tennessee Institutional Animal Care and Use Committee (Protocol #1690-1007). Water for holding fish and conducting experiments (hereafter referred to as fish water) consisted of MilliQ water (Millipore, Bedford, MA) with ions added: 19 mg/L NaHCO3, 1 mg/L sea salt (Instant Ocean Synthetic Sea Salt, Mentor, OH), 10 mg/L CaSO4, 10 mg/L MgSO4, 2 mg/L KCl. Embryos were obtained by spawning adult fish with no history of contaminant exposure. Fertilization of embryos took place at the same time (± 15 min.), such that larvae used in experiments were of similar age at the time of exposure. All activities (maintenance of adult fish, spawning, and experiments) were conducted in an environmental chamber with a temperature of 27± 1 ºC and 14:10h light:dark photoperiod. Experiment Overall Design: At 72 h post-fertilization, zebrafish larvae were exposed to lyophilized Microcystis and purified MC-LR at concentrations of 100 and 1,000 µg/L. Controls consisted of zebrafish system water (negative control) and zebrafish system water containing 0.05% ethanol (vehicle control). Larvae from both control groups as well as 100 µg/L MC-LR, 1,000 µg/L MC-LR, and lyophilized Microcystis were exposed in groups of 50 with three replicates and were sacrificed after 96 hours for total RNA extraction and subsequent microarray analysis. All larvae were exposed in beakers containing 100 ml of solution. Experiment Overall Design: Water samples for microcystin analysis and water quality measurements were taken during the experiment, and mortality and behavioral observations were recorded at 24-hour intervals. Microcystin analysis was conducted by protein phosphatase inhibition assay. Measured concentrations of microcystin-LR were 140 ± 12 SD (low concentration) and 1,703 ± 71 SD (high concentration). The concentration of microcystin-LR in the lyophilized Microcystis treatment was 4.5 µg/L. Water quality parameters measured included dissolved oxygen (6.7 mg/L), pH (6.9), total alkalinity (36 mg/L as CaCO3), total hardness (18 mg/L as CaCO3), and ammonia (<0.2 mg/L). No significant mortality or behavioral changes in larvae were observed during the exposure.
2009-08-07 | E-GEOD-12214 | biostudies-arrayexpress
Project description:Human hepatocytes, HepaRG cells and HCC HepG2 cells were treated with 50nM of Microcystin-LR and cylindrospermopsin (CYN) to observe changes in gene expression.
2023-05-12 | E-MTAB-12881 | biostudies-arrayexpress
Project description:To gain a better understanding of the mechanisms associated with the differences in the individual response to METH and thereby, further develop a list of candidate genes and pathways of possible relevance to human stimulant dependence, mania and psychosis, we conducted the present study. Rats were treated acutely with either METH or saline and their behavior measured for 3 hours after drug administration. METH treated rats were divided into high responders (HR) and low responders (LR) based on their stereotypy response. We compared gene expression between HR and LR and between these two groups and saline control.
2007-01-04 | E-MEXP-948 | biostudies-arrayexpress
Project description:Here, we performed the first iTRAQ-based proteomic analysis of early embryonic longissimus dorsi muscle from Landrance (LR) and miniature pig (Wuzhishan WZS) ranging from 21 to 42 days post coitus (dpc). 4431 proteins were identified. In both WZS and LR, the largest amount of differentially expressed proteins (DEPs) were found between 28 and 35 dpc. 252 breed-DEPs were selected by GO analysis, including 8 myofibrillar proteins. Only MYHCⅠ/IIA mRNA were detected due to early embryonic stages, and significantly higher expression of them were found in WZS during these 4 stages. MYHCⅠ was first found in WZS at 28 dpc and expressed in both breeds at later stages, while MYHCII protein was not detected until 35 dpc in both breeds. Thus, 33 myogenic breed-DEPs selected from last two stages were analyzed by STRING, which showed that some myofibrillar proteins (MYH1, TPM4, MYH10, et.al) and functional proteins (CSRP2, CASQ2, OTC, et.al), together with candidate myogenic proteins (H3F3A, HDGFRP2, et.al), probably participate in the regulatory network of myofiber formation. Thus, our study provides new data on myofiber type development during early embryo stages, which contributes to the improved understanding in the regulation mechanism of early myogenesis in agricultural animals.
2016-02-26 | PXD002481 | Pride
Project description:Farmed fish are unavoidably exposed to husbandry-related stressors which can result in outbreaks of disease, reduced reproductive success and poor growth. Biomarkers are needed for the establishment of selective breeding approaches for the production of stress resistant fish. In this context, microarray analysis has been carried out on liver tissues of two genetic lines of rainbow trout, high responders (HR) and low responders (LR), after confinement for various time periods. Microarray hybridisations provided gene expression profiles for 10 individual fish (5 of the HR line and 5 of the LR line) after 168h of confinment stress. Keywords : stress response, individual variation, fixed time point, comparison of two lines All 10 samples were hybridised against a common reference source that contained equal amounts of all 10 samples. Each sample was hybridised twice against this reference using a dye-swap setup.
2010-11-24 | E-GEOD-25440 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25440: Individual variation in confinement response at 168h GSE25473: Time course study of confinement stress in HR and LR trout lines Refer to individual Series
2010-11-24 | E-GEOD-25584 | biostudies-arrayexpress
Project description:Mocetinostat (MGCD) which is a kind of histone deacetylase inhibitors (HDACi) promotes human embryonic stem cells (hESCs) differentiation towards neural progenitor cells (NPCs). Application of HDAC inhibitors (HDACi) increased the expression of neuroectodermal markers once neural differentiation was initiated, thereby leading to more NPC generation. We used microarrays to detail the global gene expression during NPC differentiaton upon MGCD treatment and identified the transcript changes effected by MGCD during this process. Undifferentiated H9 hESCs (D0), as well as H9 cells with or without MGCD treatment on day 3 (D3C and D3M) and on day 7(D7C and D7M) of NPC generation were collected for RNA extraction and hybridization on Affymetrix microarrays.
2014-09-03 | E-GEOD-61050 | biostudies-arrayexpress
Project description:To develop an in vitro model for developmental toxicity testing, we characterized gene expression changes during mouse embryonic stem cell (mESC) differentiation and their modulation by developmental toxicants. C57BL/6 mESCs were allowed to differentiate spontaneously and global gene expression changes were studied using microarrays at at different time points after embryoid body (EB) formation. Develpmental toxicants tested include 2.0 mM monobutyl phthalate (MBP), 0.25 mM thalidomide (THD), and 1.0 mM valproic acid (VPA). RNA of control samples (unexposed) was collected at 0, 24, 48, 72, 96, 120 and 168 h after EB formation; RNA of compound-exposed samples were collected at 24 h after EB formation. Three replicates were included for each experimental condition.
2014-09-09 | E-GEOD-60174 | biostudies-arrayexpress
Project description:Farmed fish are unavoidably exposed to husbandry-related stressors which can result in outbreaks of disease, reduced reproductive success and poor growth. Biomarkers are needed for the establishment of selective breeding approaches for the production of stress resistant fish. In this context, microarray analysis has been carried out on liver tissues of two genetic lines of rainbow trout, high responders (HR) and low responders (LR), after confinement for various time periods. Microarray hybridisations provided gene expression profiles for pools of fish (stress: n=5; control: n=3) after 6h, 24h and 168h of confinement stress. Keywords : stress response, pools, time course, comparison of two lines. Samples were hybridised directly to each other in a parallel loop design. Each treatment (LC, LS, HC, HS) was hybidised in a loop of all 3 time points and each treatment loop was interconnected by hybridisations at a specific time. The publication will have this figure.
2010-11-24 | E-GEOD-25473 | biostudies-arrayexpress