Effects of the amino acid constituents of microcystin variants on cytotoxicity to primary cultured rat hepatocytes

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 t...

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Bibliographic Details
Published in:Toxins 2013-12, Vol.6 (1), p.168-179
Main Authors: Shimizu, Kumiko, Sano, Tomoharu, Kubota, Reiji, Kobayashi, Norihiro, Tahara, Maiko, Obama, Tomoko, Sugimoto, Naoki, Nishimura, Tetsuji, Ikarashi, Yoshiaki
Format: Article
Language:English
Subjects:
Algal blooms
Amino acids
Amino Acids - chemistry
Animals
Cells, Cultured
Cytotoxicity
environmental water
Eutrophication
Hepatocytes - drug effects
Hepatocytes - metabolism
Inhibitory Concentration 50
microcystin
Microcystins
Microcystins - chemistry
Microcystins - toxicity
Phosphoprotein Phosphatases - metabolism
primary cultured rat hepatocytes
Rats
Rats, Sprague-Dawley
variants
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Summary: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.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins6010168