Document Detail


The C-terminal region of a Lys49 myotoxin mediates Ca2+ influx in C2C12 myotubes.
MedLine Citation:
PMID:  19835905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myotoxins are abundant components of snake venoms, being a significant public health problem worldwide. Among them, Lys49 phospholipase A(2) homologue myotoxins cause extensive necrosis in skeletal muscle tissue. Their mechanisms of action are still poorly understood, but there is evidence that the C-terminal region is involved in membrane damage leading to myotoxicity. To investigate the effect of the C-terminal peptide 115-129 of Agkistrodon contortrix laticinctus myotoxin on the plasma membrane of myoblasts and myotubes, the entry of Ca(2+) was monitored by fluorescence imaging, and the ensuing cytotoxicity was determined. The myotoxin synthetic peptide was found to act selectively on myotubes, which were rapidly overloaded with Ca(2+) with ensuing necrosis. The profile of intracellular Ca(2+) increase induced by the C-terminal peptide, but not by its scrambled version control, reproduces the second, prominent wave of the biphasic response documented in previous studies using whole Lys49 myotoxins. These observations provide relevant insights into the mechanism of action of this family of toxins, with implications for the understanding of their structure-function relationships.
Authors:
Mariana Cintra-Francischinelli; Paola Pizzo; Yamileth Angulo; José M Gutiérrez; Cesare Montecucco; Bruno Lomonte
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-14
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  55     ISSN:  1879-3150     ISO Abbreviation:  Toxicon     Publication Date:    2010 Feb-Mar
Date Detail:
Created Date:  2010-01-29     Completed Date:  2010-04-08     Revised Date:  2011-11-24    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  England    
Other Details:
Languages:  eng     Pagination:  590-6     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Dipartimento di Scienze Biomediche, Universitá di Padova, Padova, Italy.
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MeSH Terms
Descriptor/Qualifier:
Agkistrodon
Animals
Calcium / metabolism*
Cell Line
Cell Survival / drug effects
Mice
Muscle Fibers, Skeletal / drug effects,  metabolism*
Muscle, Skeletal / drug effects,  metabolism
Myoblasts / drug effects,  metabolism
Peptides / chemistry,  toxicity
Phospholipases A2 / toxicity*
Structure-Activity Relationship
Viper Venoms / enzymology,  toxicity*
Grant Support
ID/Acronym/Agency:
GGP06133//Telethon
Chemical
Reg. No./Substance:
0/Peptides; 0/Viper Venoms; 7440-70-2/Calcium; EC 3.1.1.4/Phospholipases A2

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


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