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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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-11-01
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| 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. |
| format | Article |
| id | doaj-art-60c8dddb38924af7a47ce55376dd0fdd |
| institution | DOAJ |
| issn | 1536-0121 |
| language | English |
| publishDate | 2012-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-60c8dddb38924af7a47ce55376dd0fdd2025-08-20T02:43:16ZengSAGE 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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