Proteomic and phosphoproteomic analysis of cellular responses in medaka fish ( Oryzias latipes) following oral gavage with microcystin-LR

Chronic and subchronic toxicity resulting from exposure to microcystins (MCs) receives increasing attention due to the risk of bioaccumulation of these toxins by aquatic animals, including fish. The mechanisms of action of MCs that target the liver, involve modifications of protein phosphorylation r...

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Bibliographic Details
Published in:	Toxicon (Oxford) Vol. 51; no. 8; pp. 1431 - 1439
Main Authors:	Mezhoud, K., Bauchet, A.L., Château-Joubert, S., Praseuth, D., Marie, A., François, J.C., Fontaine, J.J., Jaeg, J.P., Cravedi, J.P., Puiseux-Dao, S., Edery, M.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 15-06-2008 Elsevier Science
Subjects:	Anatomo-pathology Animal poisons toxicology. Antivenoms Animals Bacteriology Biological and medical sciences Caspase 3 - analysis Caspase 3 - metabolism Cytosol - metabolism Electrophoresis, Gel, Two-Dimensional Enteral Nutrition Fish Proteins - metabolism Freshwater Fundamental and applied biological sciences. Psychology Gene Expression Regulation In Situ Nick-End Labeling Liver - cytology Liver - metabolism Medical sciences Microbiology Microcystin-LR-medaka-proteomics Microcystins - toxicity Oryzias - metabolism Oryzias latipes Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains Phosphoproteins - metabolism Phosphorylation Phosphorylation - drug effects Proteomics Signal Transduction - drug effects Spectrometry, Mass, Electrospray Ionization Statistics, Nonparametric Toxicology Tritium MC-LR Phosphorylation Microcystin-LR-medaka-proteomics TRAIL EST IDA Blastp tblastn 2-D PKC NCBInr PAGE 2-DE MAPK Blast TNF Anatomo-pathology MPT NCBI EST ROS rpsblast NCBI MCs i.d Vertebrata Toxicity Pisces Cyanobacteria Proteomics Oral administration Microcystin-LR-medaka-proteomics;Phosphorylation;Anatomo-pathology Animal origin Bacteria Oryzias latipes Biological accumulation
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Summary:	Chronic and subchronic toxicity resulting from exposure to microcystins (MCs) receives increasing attention due to the risk of bioaccumulation of these toxins by aquatic animals, including fish. The mechanisms of action of MCs that target the liver, involve modifications of protein phosphorylation resulting from phosphatases 1 and 2A inhibition. Therefore, studying phosphoprotein modifications by using a specific phosphoprotein stain Pro-Q Diamond in fish liver contaminated with MC-leucine–arginine (MC-LR), the most toxic MC, should help dissecting disturbed signaling and metabolic networks. We have recently used this technology to identify several proteins that are modulated either in expression or phosphorylation in the liver of medaka following short-term exposure to MC-LR by balneation. In the present study, we have decided to use an alternative way of introducing the toxin into fish; that is by gavage (force-feeding). This was first achieved using tritiated MC-LR and allowed us to quantify the quantity of toxin incorporated into fish and to demonstrate that the toxin is mainly accumulated in liver. Afterwards a proteomics study limited to liver cytosolic proteins of contaminated animals showed that several proteins were up or down regulated either in quantity or in phosphorylation or both. Some of them had been previously detected as modified in balneation experiments but new molecules were identified as involved in signal transduction pathways activated by the toxin. In addition, in the conditions used (5 μg toxin/g body weight) anatomopathological studies supported a process of apoptonecrosis established after 24 h, which was suggested to proceed by the evolution of some of the proteins after 2 h contamination.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-0101 1879-3150
DOI:	10.1016/j.toxicon.2008.03.017