Skip Navigation



ToxSci Advance Access published online on September 1, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh267
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
82/2/620    most recent
kfh267v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Reisner, M.
Right arrow Articles by Sukenik, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reisner, M.
Right arrow Articles by Sukenik, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received April 29, 2004
Accepted July 12, 2004

Environmental Toxicology

The Cyanobacterial Toxin Cylindrospermopsin Inhibits Pyrimidine Nucleotide Synthesis and Alters Cholesterol Distribution in Mice

M. Reisner 1, S. Carmeli 2, M. Werman 3, A. Sukenik 4*

1 Department of Food Engineering and Biotechnology, Technion, Israel Institute of Technology, Haifa 32000 Israel
2 School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
3 Ministry of Health, District Health Office, Public Health Laboratory, P.O. Box 9526, Haifa, 35055, Israel
4 Israel Oceanographic and Limnological Research, Yigal Allon Kinneret Limnological Laboratory, P.O. Box 447, Gigdal 14950, Israel

* To whom correspondence should be addressed. E-mail: assaf{at}ocean.org.il.


  Abstract

The hepatotoxin Cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. Our previous studies on the toxicity of cylindrospermopsin and its derivatives suggested that the uracil moiety is crucial for the toxicity and that such toxicity could partly stem from competitive binding of the toxin to a catalytic site/s involved in the synthesis of pyrimidine nucleotides (i.e. uridine). In the present study we demonstrated that cylindrospermopsin inhibited in a non-competitive manner the in vitro activity of uridine monophosphate (UMP) synthase complex (responsible for the conversion of orotic acid to UMP) in a cell free liver extract from mice, with an inhibition constant, KI, of 10 µM. Exposure of mice to cylindrospermopsin at sub acute concentrations, via drinking water, only slightly affected the in vitro activity of UMP synthase. The typical metabolic disorder associated with the inhibition of UMP synthase activity, known as "orotic aciduria", was not observed under these conditions, but other anomalous metabolic responses related to cholesterol metabolism were developed.

Keywords: hepatotoxin; cyanobacteria; cylindrospermopsin; UMP synthase; cholesterol.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.