Document Detail


Conventional apoptosis assays using propidium iodide generate a significant number of false positives that prevent accurate assessment of cell death.
MedLine Citation:
PMID:  20381494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The advent of flow cytometry-based applications has significantly impacted the study of cellular apoptosis. Propidium iodide (PI) is a commonly used viability stain in these studies. Unfortunately, we find that conventional Annexin V/PI protocols lead to a significant number of false positive events (up to 40%), which are associated with PI staining of RNA within the cytoplasmic compartment. Both primary cells and cell lines are affected, with large cells (nuclear: cytoplasmic ratios <0.5) showing the highest occurrence. This distribution spans a wide range of animal models including mice, swine, avian, and teleost fish and potentially affects up to 1016 out of 1019 of peer-reviewed papers published in this area since 1995. We show that the primary ramifications from these findings relate to cells experiencing changes in RNA content. Virally infected cells, for example, are qualified as undergoing apoptosis in response to infection based on conventional staining protocols; in fact, these cells are alive and actively producing viral RNA that can serve to produce additional infectious viral particles. Based on our observations we propose a modified protocol, show that it overcomes previous drawbacks for this technique, and that it will allow for more accurate assessment of cell death across various platforms.
Authors:
Aja M Rieger; Brian E Hall; Le Thuong Luong; Luis M Schang; Daniel R Barreda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-07
Journal Detail:
Title:  Journal of immunological methods     Volume:  358     ISSN:  1872-7905     ISO Abbreviation:  J. Immunol. Methods     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-07-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1305440     Medline TA:  J Immunol Methods     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  81-92     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthraquinones / metabolism
Apoptosis*
Cell Death
Cell Line
Cell Line, Tumor
Cell Nucleus / metabolism
Cell Survival
Cells, Cultured
Cercopithecus aethiops
Chick Embryo
Cytoplasm / metabolism
DNA / metabolism
False Positive Reactions
Flow Cytometry
Fluorescent Dyes / metabolism
Formaldehyde / metabolism
Goldfish
Humans
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Propidium / metabolism*
RNA, Double-Stranded / genetics,  metabolism
Ribonucleases / metabolism
Staining and Labeling / methods*
Sus scrofa
Tissue Fixation
Vero Cells
Virus Replication / genetics
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/1,5-bis((2-(methylamino)ethyl)amino)-4,8-dihydroxyanthracene-9,10-dione; 0/Anthraquinones; 0/Fluorescent Dyes; 0/RNA, Double-Stranded; 36015-30-2/Propidium; 50-00-0/Formaldehyde; 9007-49-2/DNA; EC 3.1.-/Ribonucleases

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


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