Differences in Toxic Response induced by three Variants of the Diarrheic Shellfish Poisoning Phycotoxins in Human Intestinal Caco-2 Cells
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PROVIDER: PRJNA668309 | ENA |
REPOSITORIES: ENA
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Project description:Diarrheic shellfish poisoning (DSP) is caused by the consumption of shellfish contaminated with a group of phycotoxins that includes okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2). These toxins are inhibitors of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A), but show distinct levels of toxicity. Aside from a difference in PP inhibition potency that would explain these differences in toxicity, others mechanisms of action are thought to be involved. Therefore, we investigated and compared which mechanisms are involved in the toxicity of these three analogues. As the intestine is one of the target organs, we studied the transcriptomic profiles of human intestinal Caco-2 cells exposed to OA, DTX-1, and DTX-2. The pathways specifically affected by each toxin treatment were further confirmed through the expression of key genes and markers of toxicity. Our results did not identify any distinct biological mechanism for OA and DTX-2. However, only DTX-1 induced up-regulation of the MAPK transduction signalling pathway, and down-regulation of gene products involved in the regulation of DNA repair. As a consequence, based on transcriptomic results, we demonstrated that the higher toxicity of DTX-1 compared to OA and DTX-2 was consistent with certain specific pathways involved in intestinal cell response.
2020-10-10 | GSE159293 | GEO
Project description:Diarrheic shellfish poisoning (DSP) is caused by the consumption of shellfish contaminated with a group of phycotoxins that includes okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2). These toxins are inhibitors of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A), but show distinct levels of toxicity. Aside from a difference in protein phosphatases (PP) inhibition potency that would explain these differences in toxicity, others mechanisms of action are thought to be involved. Therefore, we investigated and compared which mechanisms are involved in the toxicity of these three analogues. As the intestine is one of the target organs, we studied the transcriptomic profiles of human intestinal epithelial Caco-2 cells exposed to OA, DTX-1, and DTX-2. The pathways specifically affected by each toxin treatment were further confirmed through the expression of key genes and markers of toxicity. Our results did not identify any distinct biological mechanism for OA and DTX-2. However, only DTX-1 induced up-regulation of the MAPK transduction signalling pathway, and down-regulation of gene products involved in the regulation of DNA repair. As a consequence, based on transcriptomic results, we demonstrated that the higher toxicity of DTX-1 compared to OA and DTX-2 was consistent with certain specific pathways involved in intestinal cell response.
| S-EPMC7764622 | biostudies-literature
Project description:Okadaic acid (OA) is a marine biotoxin that can induce diarrheic shellfish poisoning upon consumption. It can accumulate in filter-feeding shellfish, thereby reaching the human food chain. In addition to inducing severe gastrointestinal symptoms, OA can pass the intestinal barrier into the bloodstream, thereby reaching the liver. However, the effects of OA on the liver have not been much in the focus of research so far. Therefore, this study now focuses on elucidating changes in the proteome of HepaRG cells induced by OA. Furthermore, as a potent phosphatase inhibitor, we expected changes in the phosphoproteome of the cells. Therefore, we further investigated the phosphoproteome of the HepaRG cells after OA exposure. Results revealed changes in enzyme activity regulation, cytoskeleton organization and energy metabolism.
2024-06-06 | PXD048968 | Pride
Project description:Clostridium perfringens type A is a common source of food poisoning in humans. Vegetative cells sporulate in the small intestinal tract and produce a major pathogenic factor, C. perfringens enterotoxin (CPE) during sporulation. Although sporulation plays a critical role in the pathogenesis of food poisoning, the mechanisms to induce in vivo sporulation remain unclear. Bile salts had been identified to mediate sporulation, and we have confirmed deoxycholate (DCA)-induced sporulation in C. perfringens strain NCTC8239 co-cultured with human intestinal epithelial Caco-2 cells. In this study, we performed global transcriptome analysis of strain NCTC8239 to elucidate the mechanism to induce sporulation by DCA.
2016-03-13 | GSE69649 | GEO
Project description:Clostridium perfringens type A is a common source of food poisoning in humans. Vegetative cells sporulate in the small intestinal tract and produce a major pathogenic factor, C. perfringens enterotoxin (CPE) during sporulation. Although sporulation plays a critical role in the pathogenesis of food poisoning, the mechanisms to induce in vivo sporulation remain unclear. Bile salts had been identified to mediate sporulation, and we have confirmed deoxycholate (DCA)-induced sporulation in C. perfringens strain NCTC8239 co-cultured with human intestinal epithelial Caco-2 cells. In this study, we performed global transcriptome analysis of strain NCTC8239 to elucidate the mechanism to induce sporulation by DCA. From the 55 contigs of C. perfringens strain NCTC8239, 2778 coding sequences were extracted. We designed a DNA probe by utilizing eArray provided by Agilent Technologies. The custom 8Ã15K oligonucleotide array, containing 60 mer oligonucleotide probes for 2,778 genes in strain NCTC8239, 2 bacterial control genes: 16S rRNA and 23S rRNA, and 3 human control genes: beta-2-microglobulin, glucuronidase beta and 18S rRNA, were ordered to Agilent Technologies. Each probe was spotted in five-fold on each microarray. Each strain was run in triplicate or quadruplicate.
2016-03-13 | E-GEOD-69649 | biostudies-arrayexpress
Project description:Effluent from geoduck clam larval rearing tanks at two different pH (8.2 and 7.1) was collected at 4 time points (Days 1, 5, 8, and 12) over 12 days in a shellfish hatchery in Washington state, USA. The water was filtered to 0.2 microns to retain the bacterial fraction.
2021-04-21 | PXD020692 | Pride
Project description:Okadaic acid (OA) is a widely distributed marine toxin produced by several phytoplank-tonic species and responsible for diarrheic shellfish poisoning in humans. At the molecular level OA is a specific inhibitor of several types of serine/threonine protein phosphatases.However, the underlying regulatory mechanisms involved in OA-induced cytotoxicity are not well understood. In the present study, we applied a toxicogenomic approach to investigate the effects of OA on gene expression in the human neuroblastoma line SH-SY5Y.
2017-05-23 | GSE99140 | GEO
Project description:Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Thus, the use of P(1)-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-122]
2012-01-27 | E-BUGS-122 | biostudies-arrayexpress
Project description:phytoplankton isolated from shellfish intestines metagenome Raw sequence reads
| PRJNA689099 | ENA
Project description:Transcriptional analysis of a clinical case of acute dioxin poisoning. Tissue sampling : patient 5 months and patient 11 months : skin biopsieson the face under general anaesthesia; controls 1-4 : retroauricular skin biopsies under local anaesthesia
2012-03-30 | E-MTAB-617 | biostudies-arrayexpress