Comparison of Protein Phosphatase Inhibitory Activities and Acute Toxicity of Microcystins
Date Issued
2005-07-31
Date
2005-07-31
Author(s)
DOI
932313B002059
Abstract
Eight naturally purified microcystins (MCs), including MC-LR, MC-FR,
MC-WR, MC-RR, [D-Asp3] MC-FR, [D-Asp3] MC-WR, [D-Asp3] MC-RR and [Dha7]
MC-RR were utilized to determine the effects of amino acid substitutions and
modifications on the MC-induced phosphatase inhibitory activity and animal toxicity.
It was found that the replacement of the non-polar amino acid L-leucine at the second
position of these heptacyclic peptide toxins by a polar L-arginine greatly reduced their
animal toxicities and inhibitory activities against protein phosphatase 1 (PP-1) and 2A
(PP-2A). Demethylation of methyldehydroalanine at the seventh amino acid position
of MC-RR showed the least animal toxicity and phosphatases inhibition. The loss of
methyl group on the common methylaspartic acid (MeAsp) at the third position of
MCYST-FR, MCYST-WR and MCYST-RR did not alter their toxicity levels, but
significantly reduced their activities in PP-1 inhibition. It suggests that the methyl
group on MeAsp is essential in PP-1 inhibition for MCs. However, such a tendency
was not observed in the assay of PP-2A activity. Comparing the LD50 of the mouse
toxicity assay and IC50 of the PP-1 and PP-2A inhibition assay of eight forms of
microcystins by linear correlation, it was clearly demonstrated that the MC-induced
toxicity is much more related to the inhibition of PP-2A than PP-1. These results
suggest that PP-2A inhibition plays a major role in the MC-induced toxicity.
Publisher
臺北市：國立臺灣大學漁業科學研究所
Type
journal article
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