5-aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced friend erythroleukemic cells

Malik, Zvi; Djaldetti, M

doi:10.1016/0045-6039(79)90049-6

Cited by 57 publications

(20 citation statements)

References 13 publications

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“…While the addition of ALA stimulates heme synthesis in uninduced Friend cells (indicating that ALA synthase is limiting), it does not do so in induced cells. This finding and the previous report of Malik and Djaldetti (1979) indicate that the mode of control of heme synthesis changes during erythroid differentiation.…”

Section: Discussionsupporting

confidence: 57%

Control of heme synthesis during Friend cell differentiation: Role of iron and transferrin

Laskey

Ponka

Schulman

1986

Journal Cellular Physiology

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In many types of cells the synthesis of delta-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from our laboratory with reticulocytes suggest that the rate of iron uptake from transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels of Fe-Tf (20 microM). Furthermore, in induced Friend cells 100 microM Fe-SIH stimulated 2-14C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. In contrast, Fe-SIH, even when added in high concentrations, did not stimulate heme synthesis in uninduced Friend cells but was able to do so as early as 24 to 48 h following induction. In addition, contrary to previous results with rabbit reticulocytes, Fe-SIH also stimulated globin synthesis in induced Friend cells above the level seen with saturating concentrations of transferrin. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells.

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Section: Discussionsupporting

confidence: 57%

Control of heme synthesis during Friend cell differentiation: Role of iron and transferrin

Laskey

Ponka

Schulman

1986

Journal Cellular Physiology

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“…In addition, ALA-PDT has been suggested for treating mycosis fungoides [5] and ablation of the endometrium as an alternative to hysterectomy or for sterilization [6]. The potential of topical ALA-PDT for treatment of plaque psoriasis has also been demonstrated [7,8].…”

Section: Introductionmentioning

confidence: 98%

Treatment of viral infections with 5-aminolevulinic acid and light

et al. 1997

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“…The second rate limiting step in haem synthesis is the incorporation of ferrous iron into protoporphyrin IX (PPIX), a reaction catalysed by the enzyme ferrochelatase. Owing to this slow conversion of PPIX to haem (Pottier et al, 1986) when exogenous ALA is administered, high tissue levels of porphyrin intermediates are found (Malik and Djaldetti, 1979;Sinna et al, 1981).…”

mentioning

confidence: 99%

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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5-aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced friend erythroleukemic cells

Cited by 57 publications

References 13 publications

Control of heme synthesis during Friend cell differentiation: Role of iron and transferrin

Control of heme synthesis during Friend cell differentiation: Role of iron and transferrin

Treatment of viral infections with 5-aminolevulinic acid and light

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

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