Plant toxin treatment of neonatal mouse cholangiocytes
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PROVIDER: PRJNA564001 | ENA |
REPOSITORIES: ENA
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Project description:Extrahepatic bile ducts were isolated from mouse pups at days 0-3 and primary cholangiocytes were isolated. Cholangiocytes were treated with DMSO, bilatresone (TOX4), betavulgarin (TOX2), and isoflavanone (TOX3), as per Lorent et al, Science Translationa Medicine 2015;286:286ra67 (Fig. 1), all in DMSO. Treatment concentrations were 2.0 micrograms/ml, for 6 hours.
2020-01-01 | GSE136895 | GEO
Project description:Effects of C3 toxin on RNA profiles in neonatal rat ventricular cardiac myocytes exposed to endothelin-1 (1 h)
2010-05-25 | E-MEXP-1977 | biostudies-arrayexpress
Project description:Global Gene expression changes in cholangiocytes with TGF beta treatment
| PRJNA606585 | ENA
Project description:Background & aimsBiliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to result from a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in biliary atresia in Australian livestock, but is found in a limited location and is unlikely to be a significant human toxin. We hypothesized that other unsaturated carbonyl compounds, some with the potential for significant human exposure, might also be biliary toxins.MethodsWe focused on the family of microcystins, cyclic peptide toxins from blue-green algae that are found worldwide, particularly during harmful algal blooms. We used primary extrahepatic cholangiocyte spheroids and extrahepatic bile duct explants from both neonatal [a total of 86 postnatal day (P) 2 mouse pups and 18 P2 rat pups (n = 8-10 per condition for both species)] and adult rodents [a total of 31 P15-18 mice (n = 10 or 11 per condition)] to study the biliary toxicity of microcystins and potential mechanisms involved.ResultsResults showed that 400 nM microcystin (MC)-RR, but not six other microcystins or the related algal toxin nodularin, caused >80% lumen closure in cell spheroids made from extrahepatic cholangiocytes isolated from 2-3-day-old mice (p <0.0001). By contrast, 400 nM MC-RR resulted in less than an average 5% lumen closure in spheroids derived from neonatal intrahepatic cholangiocytes or cells from adult mice (p = 0.4366). In addition, MC-RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice (p <0.0001), but not 18-day-old mice. MC-RR also caused a 2.3-times increase in reactive oxygen species in neonatal cholangiocytes (p <0.0001), and treatment with N-acetyl cysteine partially prevented microcystin-RR-induced lumen closure (p = 0.0004), suggesting a role for redox homeostasis in its mechanism of action.ConclusionsWe identified MC-RR as a selective neonatal extrahepatic cholangiocyte toxin and suggest that it acts by increasing redox stress.Impact and implicationsThe plant toxin biliatresone causes a biliary atresia-like disease in livestock and vertebrate animal model systems. We tested the widespread blue-green algal toxin, microcystin-RR, another highly electrophilic unsaturated carbonyl compound that is released during harmful algal blooms, and found that it was also a biliary toxin with specificity for neonatal extrahepatic cholangiocytes. This work should drive further animal studies and, ultimately, studies to determine whether human exposure to microcystin-RR causes biliary atresia.
| S-EPMC11648759 | biostudies-literature
Project description:wastewater treatment plant Raw sequence reads
| PRJNA1085780 | ENA
Project description:Wastewater treatment plant Raw sequence reads
| PRJNA1049605 | ENA
Project description:The present study used microarray approach to identify the genomewide response to cholera toxin in the presence of nitrate. Considering that fact that the possibility of the existence of multiple Gα genes/proteins in plants has not been conclusively ruled out, analysis of the genomewide impact of RGA1 mutation in rice and GPA1 mutation in Arabidopsis reveal only those genes that are under their direct control. On the other hand, assuming that all those different Gα subunits in any given plant are regulated by cholera toxin, analysis of the genomwide response to cholera toxin could capture the entire G-protein responsive transcriptome, beyond what can be revealed by the mutant approach. This could reveal even those genes that respond to other, as yet unidentified Gα subunits, as well as reveal some genes that are non-specifically regulated by cholera toxin, independent of any G-proteins.
2010-12-01 | GSE20924 | GEO
Project description:cholangiocytes treated with TGFbeta
| PRJNA606515 | ENA
Project description:Hospital wastewater treatment plant Metagenome
| PRJNA1010860 | ENA
Project description:Growth factor, TGF beta can have profound effect on global gene expression changes. Since TGF beta signalling is not well studied in liver epithelia , we decided to do Next gen RNA-seq analysis to look at TGF beta signaling in cholangiocytes
2020-02-20 | GSE145271 | GEO