Analytical and functional characterization of microcystins [Asp3]MC-RR and [Asp3,Dhb7]MC-RR : consequences for risk assessment?

Höger, Stefan J.; Schmid, Daniela; Blom, Judith F.; Ernst, Bernhard; Dietrich, Daniel R.

doi:10.1021/es062681p

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Analytical and functional characterization of microcystins [Asp3]MC-RR and [Asp3,Dhb7]MC-RR : consequences for risk assessment?

Type of Publication:	Journal article
URI (citable link):	http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-50379
Author:	Höger, Stefan J.; Schmid, Daniela; Blom, Judith F.; Ernst, Bernhard; Dietrich, Daniel R.
Year of publication:	2007
Published in:	Environmental Science & Technology ; 41 (2007), 7. - pp. 2609-2616. - ISSN 0013-936X. - eISSN 1520-5851
DOI (citable link):	https://dx.doi.org/10.1021/es062681p
Summary:	The microcystin (MC) producing P. rubescens occurs in pre-alpine lakes and may impact fishery success, bathing, and raw water quality. P. rubescens extracts, characterized via LC-MS, contained the two MC-RR variants [Asp3]MC-RR and [Asp3,Dhb7]MC-RR. The protein-phosphatase-inhibition assay (cPPIA with phosphatases 1 and 2A) in its capability to quantify [Asp3]MC-RR, [Asp3,Dhb7]MC-RR, and MC-RR was compared to HPLC-DAD and anti-Adda-ELISA. The IC50 values (PP1 and PP2A) determined for MC-LR, MC-RR, and [Asp3]MC-RR were in the same range (1.9-3.8 and 0.45-0.75 nM). A 50-fold higher concentration of [Asp3,Dhb7]MC-RR (29.8 nM) was necessary to inhibit the PP2A by 50%. The PP1-IC50 of [Asp3,Dhb7]MC-RR was 22-fold higher (56.4 nM) than those of the other MCs, suggesting that specific structural characteristics are responsible for its weaker PPI capacity. Western blots demonstrated that [Asp3,Dhb7]MC-RR does not covalently bind to PP1. [Asp3,Dhb7]MC-RR has comparable in vivo LD50 values to MC-RR, despite a far lower PP-inhibiting capacity, suggesting that toxicodynamic and toxicokinetic characteristics of [Asp3,Dhb7]MC-RR are responsible for its high in vivo toxicity. The data demonstrate that cPPIA analysis of [Asp3,Dhb7]MC-RR-containing samples prevent reliable MC determination and lead to underestimation of potential toxicity.
Subject (DDC):	570 Biosciences, Biology
Link to License:	In Copyright
Bibliography of Konstanz:	Yes

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HÖGER, Stefan J., Daniela SCHMID, Judith F. BLOM, Bernhard ERNST, Daniel R. DIETRICH, 2007. Analytical and functional characterization of microcystins [Asp3]MC-RR and [Asp3,Dhb7]MC-RR : consequences for risk assessment?. In: Environmental Science & Technology. 41(7), pp. 2609-2616. ISSN 0013-936X. eISSN 1520-5851. Available under: doi: 10.1021/es062681p

@article{Hoger2007Analy-8407, title={Analytical and functional characterization of microcystins [Asp3]MC-RR and [Asp3,Dhb7]MC-RR : consequences for risk assessment?}, year={2007}, doi={10.1021/es062681p}, number={7}, volume={41}, issn={0013-936X}, journal={Environmental Science & Technology}, pages={2609--2616}, author={Höger, Stefan J. and Schmid, Daniela and Blom, Judith F. and Ernst, Bernhard and Dietrich, Daniel R.} }

application/pdf Ernst, Bernhard Dietrich, Daniel R. 2011-03-24T17:43:22Z Blom, Judith F. Analytical and functional characterization of microcystins [Asp3]MC-RR and [Asp3,Dhb7]MC-RR : consequences for risk assessment? Ernst, Bernhard Schmid, Daniela Dietrich, Daniel R. First publ. in: Environmental Science & Technology ; 41 (2007), 7. - S. 2609 -2616 Höger, Stefan J. The microcystin (MC) producing P. rubescens occurs in pre-alpine lakes and may impact fishery success, bathing, and raw water quality. P. rubescens extracts, characterized via LC-MS, contained the two MC-RR variants [Asp3]MC-RR and [Asp3,Dhb7]MC-RR. The protein-phosphatase-inhibition assay (cPPIA with phosphatases 1 and 2A) in its capability to quantify [Asp3]MC-RR, [Asp3,Dhb7]MC-RR, and MC-RR was compared to HPLC-DAD and anti-Adda-ELISA. The IC50 values (PP1 and PP2A) determined for MC-LR, MC-RR, and [Asp3]MC-RR were in the same range (1.9-3.8 and 0.45-0.75 nM). A 50-fold higher concentration of [Asp3,Dhb7]MC-RR (29.8 nM) was necessary to inhibit the PP2A by 50%. The PP1-IC50 of [Asp3,Dhb7]MC-RR was 22-fold higher (56.4 nM) than those of the other MCs, suggesting that specific structural characteristics are responsible for its weaker PPI capacity. Western blots demonstrated that [Asp3,Dhb7]MC-RR does not covalently bind to PP1. [Asp3,Dhb7]MC-RR has comparable in vivo LD50 values to MC-RR, despite a far lower PP-inhibiting capacity, suggesting that toxicodynamic and toxicokinetic characteristics of [Asp3,Dhb7]MC-RR are responsible for its high in vivo toxicity. The data demonstrate that cPPIA analysis of [Asp3,Dhb7]MC-RR-containing samples prevent reliable MC determination and lead to underestimation of potential toxicity. 2007 Blom, Judith F. terms-of-use eng Schmid, Daniela Höger, Stefan J.