Ceramide aminoethylphosphonate from jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin
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ORIGINAL ARTICLE
Chemistry and Biochemistry
Ceramide aminoethylphosphonate from jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin-LR Masaharu Komatsu • Naoki Ichiyama • Takashi Kurimoto • Shota Takumi Kazuhiro Shiozaki • Yasumasa Sugiyama • Tatsuhiko Furukawa • Seiichi Ando • Saki Itonori • Hiroaki Saito
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Received: 11 October 2012 / Accepted: 20 December 2012 / Published online: 11 January 2013 Ó The Japanese Society of Fisheries Science 2013
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
M. Komatsu (&) N. Ichiyama T. Kurimoto K. Shiozaki Y. Sugiyama Department of Food and Chemical Biology, Faculty of Fisheries, Kagoshima University, Shimoarata 4-50-20, Kagoshima 890-0056, Japan e-mail: [email protected] S. Takumi Center for Environmental Health Sciences, National Institution of Environmental Studies, Tsukuba, Ibaraki, Japan T. Furukawa Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan S. Ando Department of Nutritional Sciences, Faculty of Health and Welfare Science, Nayoro City University, Nayoro, Hokkaido, Japan S. Itonori Department of Chemistry, Faculty of Liberal Arts and Education, Shiga University, Otsu, Shiga, Japan H. Saito Applied Biochemistry Section, Biochemistry and Food Technology Division, National Research Institute of Fisheries Science, Fisheries Research Agency, Yokohama, Kanagawa, Japan
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. Keywords Chemical prevention Ceramide aminoethylphosphonate Cytotoxicity Microcystin-LR OATP1B3
Introduction Microcystin-LR is a cyclic peptide released by several bloom-forming toxic cyanobacteria [1]. Understanding the toxicity of microcystin-LR is of paramount importance, because of both its potency with its acute cytotoxicity and its tumor-promoting activity in hepatocytes of animals and humans [2, 3]. Microcystin-LR toxici
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