Document Detail


Imaging reversal of multidrug resistance in living mice with bioluminescence: MDR1 P-glycoprotein transports coelenterazine.
MedLine Citation:
PMID:  14755051     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Coelenterazine is widely distributed among marine organisms, producing bioluminescence by calcium-insensitive oxidation mediated by Renilla luciferase (Rluc) and calcium-dependent oxidation mediated by the photoprotein aequorin. Despite its abundance in nature and wide use of both proteins as reporters of gene expression and signal transduction, little is known about mechanisms of coelenterazine transport and cell permeation. Interestingly, coelenterazine analogues share structural and physiochemical properties of compounds transported by the multidrug resistance MDR1 P-glycoprotein (Pgp). Herein, we report that living cells stably transfected with a codon-humanized Rluc show coelenterazine-mediated bioluminescence in a highly MDR1 Pgp-modulated manner. In Pgp-expressing Rluc cells, low baseline bioluminescence could be fully enhanced (reversed) to non-Pgp matched control levels with potent and selective Pgp inhibitors. Therefore, using coelenterazine and noninvasive bioluminescence imaging in vivo, we could directly monitor tumor-specific Pgp transport inhibition in living mice. While enabling molecular imaging and high-throughput screening of drug resistance pathways, these data also raise concern for the indiscriminate use of Rluc and aequorin as reporters in intact cells or transgenic animals, wherein Pgp-mediated alterations in coelenterazine permeability may impact results.
Authors:
Andrea Pichler; Julie L Prior; David Piwnica-Worms
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2004-01-30
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  101     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-11     Completed Date:  2004-04-09     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1702-7     Citation Subset:  IM    
Affiliation:
Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Drug Resistance, Multiple*
Imidazoles*
Luminescent Measurements
Mice
P-Glycoprotein / metabolism*
Pyrazines / metabolism*
Transfection
Grant Support
ID/Acronym/Agency:
P50 CA 94056/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Imidazoles; 0/P-Glycoprotein; 0/Pyrazines; 55779-48-1/coelenterazine
Comments/Corrections

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


Previous Document:  Localised genital Norwegian scabies in an AIDS patient.
Next Document:  Histone H3 lysine 9 methylation is required for DNA elimination in developing macronuclei in Tetrahy...