Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line
δ-aminolevulinic acid (ALA) is the precursor in the biosynthesis of porphyrins. The knowledge of both the regulation of ALA entrance and efflux from the cells and the control of porphyrin biosynthesis is essential to improve ALA-mediated photodynamic therapy. In this work, we studied the regulation...
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2003
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paper:paper_00070920_v89_n1_p173_CorreaGarcia2023-06-08T14:31:34Z Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line Correa García, Susana Raquel Casas, Adriana Gabriela Perotti, Christian Pablo Batlle, Alcira María del Carmen Bermudez Moretti, Mariana δ-aminolevulinic acid ALA efflux ALA uptake Photodynamic therapy 4 aminobutyric acid aminolevulinic acid heme derivative porphobilinogen porphyrin succinylacetone animal cell article breast adenocarcinoma cancer cell culture cell transport controlled study diffusion heme synthesis mouse nonhuman photodynamic therapy priority journal protein function protein protein interaction protein transport temperature dependence Adenocarcinoma Aminolevulinic Acid Animals gamma-Aminobutyric Acid Mammary Neoplasms, Animal Mice Photochemotherapy Photosensitizing Agents Porphyrins Tumor Cells, Cultured δ-aminolevulinic acid (ALA) is the precursor in the biosynthesis of porphyrins. The knowledge of both the regulation of ALA entrance and efflux from the cells and the control of porphyrin biosynthesis is essential to improve ALA-mediated photodynamic therapy. In this work, we studied the regulation of ALA uptake and efflux by endogenously accumulated ALA and/or porphyrins in murine mammary adenocarcinoma cells. Under our set of conditions, the haem synthesis inhibitor succinyl acetone completely prevented porphobilinogen and porphyrin synthesis from ALA, and led to an increase in the intracellular ALA pool. However, neither intracellular ALA nor porphyrin pools regulate ALA uptake or efflux during the first 15 min of the process. Based on temperature dependence data, ALA but not γ-aminobutyric acid (GABA) efflux is mediated by a diffusion mechanism. Moreover, the addition of extracellular GABA not only did not influence the rate of ALA efflux but on the contrary it affected ALA uptake, showing the contribution of a saturable mechanism for the uptake, but not for the efflux of ALA from the cells. © 2003 Cancer Research UK. Fil:Correa García, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Perotti, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bermúdez Moretti, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00070920_v89_n1_p173_CorreaGarcia http://hdl.handle.net/20.500.12110/paper_00070920_v89_n1_p173_CorreaGarcia |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
δ-aminolevulinic acid ALA efflux ALA uptake Photodynamic therapy 4 aminobutyric acid aminolevulinic acid heme derivative porphobilinogen porphyrin succinylacetone animal cell article breast adenocarcinoma cancer cell culture cell transport controlled study diffusion heme synthesis mouse nonhuman photodynamic therapy priority journal protein function protein protein interaction protein transport temperature dependence Adenocarcinoma Aminolevulinic Acid Animals gamma-Aminobutyric Acid Mammary Neoplasms, Animal Mice Photochemotherapy Photosensitizing Agents Porphyrins Tumor Cells, Cultured |
spellingShingle |
δ-aminolevulinic acid ALA efflux ALA uptake Photodynamic therapy 4 aminobutyric acid aminolevulinic acid heme derivative porphobilinogen porphyrin succinylacetone animal cell article breast adenocarcinoma cancer cell culture cell transport controlled study diffusion heme synthesis mouse nonhuman photodynamic therapy priority journal protein function protein protein interaction protein transport temperature dependence Adenocarcinoma Aminolevulinic Acid Animals gamma-Aminobutyric Acid Mammary Neoplasms, Animal Mice Photochemotherapy Photosensitizing Agents Porphyrins Tumor Cells, Cultured Correa García, Susana Raquel Casas, Adriana Gabriela Perotti, Christian Pablo Batlle, Alcira María del Carmen Bermudez Moretti, Mariana Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
topic_facet |
δ-aminolevulinic acid ALA efflux ALA uptake Photodynamic therapy 4 aminobutyric acid aminolevulinic acid heme derivative porphobilinogen porphyrin succinylacetone animal cell article breast adenocarcinoma cancer cell culture cell transport controlled study diffusion heme synthesis mouse nonhuman photodynamic therapy priority journal protein function protein protein interaction protein transport temperature dependence Adenocarcinoma Aminolevulinic Acid Animals gamma-Aminobutyric Acid Mammary Neoplasms, Animal Mice Photochemotherapy Photosensitizing Agents Porphyrins Tumor Cells, Cultured |
description |
δ-aminolevulinic acid (ALA) is the precursor in the biosynthesis of porphyrins. The knowledge of both the regulation of ALA entrance and efflux from the cells and the control of porphyrin biosynthesis is essential to improve ALA-mediated photodynamic therapy. In this work, we studied the regulation of ALA uptake and efflux by endogenously accumulated ALA and/or porphyrins in murine mammary adenocarcinoma cells. Under our set of conditions, the haem synthesis inhibitor succinyl acetone completely prevented porphobilinogen and porphyrin synthesis from ALA, and led to an increase in the intracellular ALA pool. However, neither intracellular ALA nor porphyrin pools regulate ALA uptake or efflux during the first 15 min of the process. Based on temperature dependence data, ALA but not γ-aminobutyric acid (GABA) efflux is mediated by a diffusion mechanism. Moreover, the addition of extracellular GABA not only did not influence the rate of ALA efflux but on the contrary it affected ALA uptake, showing the contribution of a saturable mechanism for the uptake, but not for the efflux of ALA from the cells. © 2003 Cancer Research UK. |
author |
Correa García, Susana Raquel Casas, Adriana Gabriela Perotti, Christian Pablo Batlle, Alcira María del Carmen Bermudez Moretti, Mariana |
author_facet |
Correa García, Susana Raquel Casas, Adriana Gabriela Perotti, Christian Pablo Batlle, Alcira María del Carmen Bermudez Moretti, Mariana |
author_sort |
Correa García, Susana Raquel |
title |
Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
title_short |
Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
title_full |
Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
title_fullStr |
Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
title_full_unstemmed |
Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
title_sort |
mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line |
publishDate |
2003 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00070920_v89_n1_p173_CorreaGarcia http://hdl.handle.net/20.500.12110/paper_00070920_v89_n1_p173_CorreaGarcia |
work_keys_str_mv |
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_version_ |
1768546424477188096 |