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Imprint
Mechanistic studies concerning the influence of okadaic acid on the intestinal barrier, the lipidperoxidation and the phosphoproteome
Project
Project code: BfR-LMS-08-1322-662
Contract period: 01.03.2016
- 31.12.2016
Purpose of research: Applied research
The lipophilic marine biotoxin okadaic acid is produced by algae of the genus Dinophysis and Prorocentrum and is the most abundant marine Biotoxin worldwide. The consumption of seafood contaminated with high concentrations of the odourless and tasteless toxin is responsible for the diarrheic shellfish poisoning syndrome (DSP) in humans. An important aspect concerning the toxicity induced by OA in high concentrations is the damage of the human intestinal barrier which leads to increased paracellular permeability. The cause for that damage of epithelial integrity remains still unclear. It is also assumed that OA is an inductor of lipidperoxidation and is responsible for the generation of free radicals. Furthermore there are indications that the phase I drug-metabolizing enzymes lead to a toxification of OA. This effect is more pronounced in human systems than in rat systems. In addition, the results of previous studies performed by Franziska Kolrep indicate that non CYP enzymes of phase I metabolism could be responsible for the biotransformation of OA and thus lead to a biological activation. It has long been known that OA is a potent inhibitor of the serine/threonine-phosphatases 1 and 2A and therefore disturbs the strongly regulated and essential equilibration of phosphorylating and dephosphorylating processes. However there are studies which could not prove that OA acts as an inhibitor of PP1. Furthermore little is known about the consequences of the inhibition of the phosphatases concerning important cellular signaling pathways. Thus it is really important to investigate the short and long term influence of OA on the phosphoproteome to assess how OA affects the two phosphatases and further cellular regulatory mechanisms. Since the risk of contamination in seafood caused by environmental pollution, shipping traffic and climatic influences is still very high and the cases of DSP poisoning rise annually, it is of enormous importance for the consumer protection to fully explain the toxic mechanism of OA. Thus, the aim of this study is to investigate the influence of OA concerning the intestinal barrier, the lipidperoxidation and the phosphoproteome to explain the molecular mode of action of OA what is necessary for a more detailed risk assessment.
Section overview
Subjects
- Toxicology
