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Open AccessArticle

Effects of the Amino Acid Constituents of Microcystin Variants on Cytotoxicity to Primary Cultured Rat Hepatocytes

1
Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
2
Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba-shi, Ibaraki 305-8506, Japan
3
Division of Food Additives, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
4
Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Nakano 4-21-2, Nakano-ku, Tokyo 164-8530, Japan
*
Author to whom correspondence should be addressed.
Toxins 2014, 6(1), 168-179; https://doi.org/10.3390/toxins6010168
Received: 13 November 2013 / Revised: 13 December 2013 / Accepted: 24 December 2013 / Published: 30 December 2013
Microcystins, which are cyclic heptapeptides produced by some cyanobacterial species from algal blooms, strongly inhibit serine/threonine protein phosphatase and are known as hepatotoxins. Microcystins have many structural variations, yet insufficient information is available on the differences in the cytotoxic potentials among the structural variants. In this study, the cytotoxicities of 16 microcystin variants at concentrations of 0.03–10 μg/mL to primary cultured rat hepatocytes were determined by measuring cellular ATP content, and subsequently determined by their 50% inhibitory concentration (IC50). Differences in the amino acid constituents were associated with differences in cytotoxic potential. [d-Asp3, Z-Dhb7] microcystin-LR exhibited the strongest cytotoxicity at IC50 of 0.053 μg/mL among the microcystin variants tested. Furthermore, [d-Asp3, Z-Dhb7] microcystin-HtyR was also highly cytotoxic. These results suggest that both d-Asp and Z-Dhb residues are important in determining the cytotoxic potential of microcystin variants. View Full-Text
Keywords: microcystin; variants; cytotoxicity; primary cultured rat hepatocytes; environmental water microcystin; variants; cytotoxicity; primary cultured rat hepatocytes; environmental water
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MDPI and ACS Style

Shimizu, K.; Sano, T.; Kubota, R.; Kobayashi, N.; Tahara, M.; Obama, T.; Sugimoto, N.; Nishimura, T.; Ikarashi, Y. Effects of the Amino Acid Constituents of Microcystin Variants on Cytotoxicity to Primary Cultured Rat Hepatocytes. Toxins 2014, 6, 168-179. https://doi.org/10.3390/toxins6010168

AMA Style

Shimizu K, Sano T, Kubota R, Kobayashi N, Tahara M, Obama T, Sugimoto N, Nishimura T, Ikarashi Y. Effects of the Amino Acid Constituents of Microcystin Variants on Cytotoxicity to Primary Cultured Rat Hepatocytes. Toxins. 2014; 6(1):168-179. https://doi.org/10.3390/toxins6010168

Chicago/Turabian Style

Shimizu, Kumiko; Sano, Tomoharu; Kubota, Reiji; Kobayashi, Norihiro; Tahara, Maiko; Obama, Tomoko; Sugimoto, Naoki; Nishimura, Tetsuji; Ikarashi, Yoshiaki. 2014. "Effects of the Amino Acid Constituents of Microcystin Variants on Cytotoxicity to Primary Cultured Rat Hepatocytes" Toxins 6, no. 1: 168-179. https://doi.org/10.3390/toxins6010168

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