Ceramide aminoethylphosphonate from jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin-LR
Ceramide aminoethylphosphonate from jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin-LR
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DOI：
10.1007/s12562-012-0593-2
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发表时间：
2013-03-01
影响因子：
1.9
通讯作者：
Saito, Hiroaki
中科院分区：
文献类型：
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作者：
Komatsu, Masaharu;Ichiyama, Naoki;Saito, Hiroaki
我们以前建立了从大鱿鱼中分离氨基乙基膦酸神经酰胺（CAEP）的方法。在本研究中，我们使用MTT法来评估CAEP对细胞系的安全性，以应用于保健食品和补充剂。CAEP对各种HEK 293转染细胞没有显示任何细胞毒性。其次，阐明了CAEP对体细胞的积极作用。近年来，我们报道了肝毒素微囊藻毒素-LR通过肝细胞摄取转运蛋白OATP 1B 1和OATP 1B 3介导被肝细胞摄取，并诱导细胞产生细胞毒性。CAEP以浓度依赖性方式优先减弱微囊藻毒素-LR对永久表达OATP 1B 3的HEK 293-OATP 1B 3细胞的细胞毒性，而不是对HEK 293-OATP 1B 1细胞的细胞毒性。此外，丝氨酸/苏氨酸磷酸酶的酶活性，这是抑制微囊藻毒素-LR，恢复共同暴露于CAEP。此外，微囊藻毒素LR诱导的细胞蛋白磷酸化被破坏的CAEP曝光。这些结果表明，CAEP是一种很有前途的补救和/或预防药物微囊藻毒素LR的肝损害。
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.