title: Effects of the amino acid constituents of microcystin variants on cytotoxicity to primary cultured rat hepatocytes.
abstract: 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.
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. kshimizu@nihs.go.jp.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. sanotomo@nies.go.jp.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Sano
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. reijik@nihs.go.jp.
authors.forename: Reiji
authors.initials: R
authors.lastname: Kubota
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. norihiro.kobayashi@nihs.go.jp.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. tahara@nihs.go.jp.
authors.forename: Maiko
authors.initials: M
authors.lastname: Tahara
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. obama@nihs.go.jp.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Obama
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. nsugimot@nihs.go.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. t.nishimura@thu.ac.jp.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. ikarashi@nihs.go.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikarashi
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008387:Marine Toxins; D052998:Microcystins / Q000737:chemistry / Q000633:toxicity*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D008387:Marine Toxins; D052998:Microcystins; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR