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    
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.
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    
Cancer Research UK Cambridge Research Institute, Li-Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom.
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MeSH Terms
Annexin A5 / chemistry*,  diagnostic use*,  metabolism
Breast Neoplasms / diagnosis
Cell Death*
Cell Line, Tumor
Fluorescent Dyes / chemistry
Lymphoma / diagnosis
Protein Binding
Protein Structure, Tertiary
Synaptotagmin I / chemistry*,  diagnostic use*,  metabolism
Grant Support
CA197/A3514//Cancer Research UK; //Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Annexin A5; 0/Fluorescent Dyes; 0/Synaptotagmin I

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