Document Detail


Cytotoxic and cytoskeletal effects of azaspiracid-1 on mammalian cell lines.
MedLine Citation:
PMID:  15904684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Azaspiracid-1 (AZA-1) is a newly identified phycotoxin reported to accumulate in molluscs from several northern European countries and documented to have caused severe human intoxications. The mechanism of action of AZA-1 is unknown. Our initial investigations have shown that AZA-1 is cytotoxic to a range of cell types. Cytotoxicity was evident in all seven cell types tested, suggesting a broad-spectrum mode of action, and was both time- and concentration-dependent. However, AZA-1 took an unusually long time (>24 h) to cause complete cytotoxicity in most cell types, with the exception of the rat pituitary GH(4)C(1). Extended exposure times did not always lower the EC(50) value for a given cell line, but always resulted in more complete cytotoxicity over a very narrow concentration range. The Jurkat cell line (human lymphocyte T) appeared to be very sensitive to AZA-1, although the EC(50) values (24-72 h) for all the cell types were in the low nanomolar range (0.9-16.8 nM). The effect of AZA-1 on membrane integrity was tested on Jurkat cells and these data confirm our visual observations of cytotoxicity and necrotic cell lysis following exposure of Jurkat cells to AZA-1 and suggest that AZA-1 has some properties unique among marine algal toxins. Additionally, there were dramatic effects of AZA-1 on the arrangement of F-actin with the concurrent loss of pseudopodia, cytoplasmic extensions that function in mobility and chemotaxis. Although these phycotoxin-specific effects of AZA-1 suggest a possible site of action, further work using cell-based approaches is needed to determine the precise mode of action of AZA-1.
Authors:
Michael J Twiner; Philipp Hess; Marie-Yasmine Bottein Dechraoui; Terry McMahon; Melissa S Samons; Masayuki Satake; Takeshi Yasumoto; John S Ramsdell; Gregory J Doucette
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-04-18
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  45     ISSN:  0041-0101     ISO Abbreviation:  Toxicon     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-20     Completed Date:  2005-09-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  England    
Other Details:
Languages:  eng     Pagination:  891-900     Citation Subset:  IM    
Affiliation:
Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, NOAA/National Ocean Service, Charleston SC 29412, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Bivalvia / chemistry
Cell Line
Cell Survival / drug effects*
Cytoskeleton / drug effects,  pathology
Humans
Jurkat Cells
Marine Toxins / toxicity*
Phosphoprotein Phosphatases / antagonists & inhibitors,  metabolism
Pseudopodia / drug effects*,  pathology
Spiro Compounds / toxicity*
Chemical
Reg. No./Substance:
0/Actins; 0/Marine Toxins; 0/Spiro Compounds; 0/azaspiracid; EC 3.1.3.16/Phosphoprotein Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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