Document Detail


Comparison of the C2A domain of synaptotagmin-I and annexin-V as probes for detecting cell death.
MedLine Citation:
PMID:  20402461     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The induction of apoptosis is frequently accompanied by the exposure of phosphatidylserine (PS) on the cell surface, which has been detected using radionuclide and fluorescently labeled derivatives of the PS-binding protein, Annexin V. The fluorescently labeled protein has been used extensively in vitro as a diagnostic reagent for detecting cell death, and radionuclide-labeled derivatives have undergone clinical trials for detecting tumor cell death in vivo following treatment. We show here that the C2A domain of Synaptotagmin-I, which had been fluorescently labeled at a single cysteine residue introduced by site-directed mutagenesis, detected the same levels of cell death as a similarly labeled Annexin-V derivative, in drug-treated murine lymphoma and human breast cancer cell lines in vitro. However, the C2A derivative showed significantly less binding to viable cells and, as a consequence, up to 4-fold more specific binding to apoptotic and necrotic cells when compared with Annexin-V. C2A offers a potential route for the development of a new generation of more specific imaging probes for the detection of tumor cell death in the clinic.
Authors:
Israt S Alam; Andre A Neves; Timothy H Witney; Joan Boren; Kevin M Brindle
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  21     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-08-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  884-91     Citation Subset:  IM    
Affiliation:
Cancer Research UK Cambridge Research Institute, Li-Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A5 / chemistry*,  diagnostic use*,  metabolism
Breast Neoplasms / diagnosis
Cell Death*
Cell Line, Tumor
Female
Fluorescent Dyes / chemistry
Humans
Lymphoma / diagnosis
Protein Binding
Protein Structure, Tertiary
Rats
Synaptotagmin I / chemistry*,  diagnostic use*,  metabolism
Grant Support
ID/Acronym/Agency:
CA197/A3514//Cancer Research UK; //Biotechnology and Biological Sciences Research Council
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Fluorescent Dyes; 0/Synaptotagmin I

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


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