Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms

Bioluminescence imaging (BLI) detects light generated by luciferase-mediated oxidation of substrate and is used widely for evaluating transgene expression in cell-based assays and in vivo in relevant preclinical models. The most commonly used luciferase for in vivo applications is firefly luciferase...

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Main Authors: Yimao Zhang, Mrudula Pullambhatla, John Laterra, Martin G. Pomper
Format: Article
Language:English
Published: SAGE Publishing 2012-11-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2012.00005
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author Yimao Zhang
Mrudula Pullambhatla
John Laterra
Martin G. Pomper
author_facet Yimao Zhang
Mrudula Pullambhatla
John Laterra
Martin G. Pomper
author_sort Yimao Zhang
collection DOAJ
description Bioluminescence imaging (BLI) detects light generated by luciferase-mediated oxidation of substrate and is used widely for evaluating transgene expression in cell-based assays and in vivo in relevant preclinical models. The most commonly used luciferase for in vivo applications is firefly luciferase (fLuc), for which D-luciferin serves as the substrate. We demonstrated previously that the expression of the ABCG2 efflux transporter can significantly reduce BLI signal output and that HhAntag-691 can inhibit the efflux of D-luciferin, thereby enhancing BLI signal. Here we show that an HhAntag-691-sensitive uptake mechanism facilitates the intracellular concentration of D-luciferin and that the BLI dynamics of different cell lines are coregulated by this uptake mechanism in conjunction with ABCG2-mediated efflux. After administration of D-luciferin, the HhAntag-691-sensitive uptake mechanism generates a rapid increase in BLI signal that decreases over time, whereas ABCG2-mediated efflux stably reduces signal output. We implicate SLC22A4 (OCTN1), a member of the organic cation/zwitterion uptake transporter family, as one potential mediator of the HhAntag-691-sensitive D-luciferin uptake. These findings provide insight into mechanisms that contribute to the cellular uptake kinetics and in vivo biodistribution of D-luciferin.
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spelling doaj-art-60c8dddb38924af7a47ce55376dd0fdd2025-01-03T00:12:14ZengSAGE PublishingMolecular Imaging1536-01212012-11-011110.2310/7290.2012.0000510.2310_7290.2012.00005Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux MechanismsYimao ZhangMrudula PullambhatlaJohn LaterraMartin G. PomperBioluminescence imaging (BLI) detects light generated by luciferase-mediated oxidation of substrate and is used widely for evaluating transgene expression in cell-based assays and in vivo in relevant preclinical models. The most commonly used luciferase for in vivo applications is firefly luciferase (fLuc), for which D-luciferin serves as the substrate. We demonstrated previously that the expression of the ABCG2 efflux transporter can significantly reduce BLI signal output and that HhAntag-691 can inhibit the efflux of D-luciferin, thereby enhancing BLI signal. Here we show that an HhAntag-691-sensitive uptake mechanism facilitates the intracellular concentration of D-luciferin and that the BLI dynamics of different cell lines are coregulated by this uptake mechanism in conjunction with ABCG2-mediated efflux. After administration of D-luciferin, the HhAntag-691-sensitive uptake mechanism generates a rapid increase in BLI signal that decreases over time, whereas ABCG2-mediated efflux stably reduces signal output. We implicate SLC22A4 (OCTN1), a member of the organic cation/zwitterion uptake transporter family, as one potential mediator of the HhAntag-691-sensitive D-luciferin uptake. These findings provide insight into mechanisms that contribute to the cellular uptake kinetics and in vivo biodistribution of D-luciferin.https://doi.org/10.2310/7290.2012.00005
spellingShingle Yimao Zhang
Mrudula Pullambhatla
John Laterra
Martin G. Pomper
Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms
Molecular Imaging
title Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms
title_full Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms
title_fullStr Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms
title_full_unstemmed Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms
title_short Influence of Bioluminescence Imaging Dynamics by D-Luciferin Uptake and Efflux Mechanisms
title_sort influence of bioluminescence imaging dynamics by d luciferin uptake and efflux mechanisms
url https://doi.org/10.2310/7290.2012.00005
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AT johnlaterra influenceofbioluminescenceimagingdynamicsbydluciferinuptakeandeffluxmechanisms
AT martingpomper influenceofbioluminescenceimagingdynamicsbydluciferinuptakeandeffluxmechanisms