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Ceramide aminoethylphosphonate from jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin-LR
Authors:Masaharu Komatsu  Naoki Ichiyama  Takashi Kurimoto  Shota Takumi  Kazuhiro Shiozaki  Yasumasa Sugiyama  Tatsuhiko Furukawa  Seiichi Ando  Saki Itonori  Hiroaki Saito
Institution:1. Department of Food and Chemical Biology, Faculty of Fisheries, Kagoshima University, Shimoarata 4-50-20, Kagoshima, 890-0056, Japan
2. Center for Environmental Health Sciences, National Institution of Environmental Studies, Tsukuba, Ibaraki, Japan
3. Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
4. Department of Nutritional Sciences, Faculty of Health and Welfare Science, Nayoro City University, Nayoro, Hokkaido, Japan
5. Department of Chemistry, Faculty of Liberal Arts and Education, Shiga University, Otsu, Shiga, Japan
6. Applied Biochemistry Section, Biochemistry and Food Technology Division, National Research Institute of Fisheries Science, Fisheries Research Agency, Yokohama, Kanagawa, Japan
Abstract:We have previously established the method for isolation of ceramide aminoethylphosphonate (CAEP) from jumbo flying squid Dosidicus gigas. In this study, we performed a MTT assay to evaluate the safety of CAEP to the cell lines for the application to health food and supplements. The CAEP did not show any cytotoxicity to various HEK293-transfectant cells. Next, we elucidated the positive function of CAEP to the somatic cells. Recently, we have reported that hepatotoxin microcystin-LR was taken up into the hepatocytes mediated by hepatocellular uptake transporters OATP1B1 and OATP1B3, and the cells were induced cytotoxicity subsequently. Cytotoxicity of microcystin-LR to permanently OATP1B3-expressing HEK293-OATP1B3 cells rather than to HEK293-OATP1B1 cells was preferentially attenuated by CAEP in a concentration-dependent manner. In addition, the enzyme activity of serine/threonine phosphatase, which was inhibited by microcystin-LR, was recuperated by co-exposure to CAEP. Furthermore, microcystin-LR-induced cellular protein phosphorylation were disrupted by CAEP exposure. These results suggested that CAEP is a promising remedy and/or preventive medicine for liver damage with microcystin-LR.
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