δ-Aminolevulinic acid transport in murine mammary adenocarcinoma cells is mediated by beta transporters

Moretti, Mariana Bermúdez; García, Sara Mallén; Perotti, Christian; Batlle, Alcira; Casas, Adriana

doi:10.1038/sj.bjc.6600481

Cited by 45 publications

(36 citation statements)

References 21 publications

(27 reference statements)

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“…On the other hand, only active transport seems to be involved in GABA efflux. These were the expected results since they are in agreement with our previous findings (Bermúdez Moretti et al, 2002), where we demonstrated that ALA is incorporated into these cells through two different mechanisms, diffusion and an active process, while GABA uptake is not mediated by diffusion.…”

Section: Discussionsupporting

confidence: 82%

“…In Figure 1A, ALA uptake was measured in cells treated with SA. We choose 0.1 mM ALA for this experiment to minimize ALA conversion (Bermúdez Moretti et al, 2002). When the cells were preincubated for 20 min with 0.5 mM SA and this compound was withdrawn before adding 14 C-ALA, ALA incorporation is similar to that found in control cells.…”

Section: Resultsmentioning

confidence: 85%

“…porphyrin synthesis up to 3 h has been previously established for this cell line (Bermúdez Moretti et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The BETA transporter family comprise GAT-1 to GAT-3, BGT-1 and TAUT transport systems (Palacín et al, 1998). Using murine mammary adenocarcinoma cultured cells, we have recently demonstrated that ALA is incorporated by two different processes (Bermúdez Moretti et al, 2002). One of these processes is passive diffusion that is significant at shorter incubation intervals.…”

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confidence: 99%

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Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line

et al. 2003

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d-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 g-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.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 85%

“…porphyrin synthesis up to 3 h has been previously established for this cell line (Bermúdez Moretti et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line

et al. 2003

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“…This suggests that their incorporation mechanisms into the cell are different, and that, whereas ALA and THP-ALA uptake appear to need a threshold concentration, He-ALA uptake takes place even at low concentrations. It has been shown that in LM3 cells ALA uptake occurs by both diffusion and active transport, the latter presumably mediated by a member of the GAT family transporters (Bermúdez Moretti et al, 2002). Here, we have evidence that He-ALA and undecanoyl-ALA are incorporated by a different transport system.…”

Section: Resultsmentioning

confidence: 51%

Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies

et al. 2004

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The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a murine mammary tumour, in tumour explants and after injection of the cells into mice. In vitro, undecanoyl-ALA and THP-ALA did not improve ALA efficacy in terms of porphyrin synthesis. On the other hand, half of the amount of ALA is required to obtain the same plateau amount of photosensitiser from He-ALA. However, this plateau value cannot be surpassed in spite of the four-times higher accumulation of ALA/He-ALA from the ALA derivative. This shows that He-ALA conversion to porphyrins but not He-ALA entry to the cells is limiting. Employing ionic exchange chromatography, we found that 80% of total uptake was He-ALA whereas only 20% was ALA. This suggests that the esterases, probably themselves regulated by the heme pathway, are limiting the conversion of ALA derivatives into porphyrins. A similar situation occurs with THP-ALA. Tumour explant porphyrin results correlate well with cell line data. However, i.p. injection of ALA derivatives to mice resulted in a lower porphyrin concentration in the tumour when compared to the administration of equimolar amounts of ALA, indicating that there should be retention of ALA derivatives either within the blood vessels in the initial phase of distribution and/or within the capillaries of the tumour.

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In vitro resistance of articular chondrocytes to 5‐Aminolevulinic acid based photodynamic therapy

et al. 2008

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δ-Aminolevulinic acid transport in murine mammary adenocarcinoma cells is mediated by beta transporters

Cited by 45 publications

References 21 publications

Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line

Mechanistic studies on δ-aminolevulinic acid uptake and efflux in a mammary adenocarcinoma cell line

Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies

In vitro resistance of articular chondrocytes to 5‐Aminolevulinic acid based photodynamic therapy

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