Regulation of amino acid transport in chick embryo heart cells

Gazzola, Gian C.; Franchi, Roberto; Saibene, V.; Ronchi, Paolo; Guidotti, Guido

doi:10.1016/0005-2736(72)90097-1

Cited by 138 publications

(31 citation statements)

References 17 publications

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“…This mechanism, named adaptive regulation or adaptive increase, was originally described in mesenchymal cells of avian origin (7), but it has also been found in many other models (5). Adaptive increase of system A transport activity is prevented by medium supplementation with a single amino acid species, such as L-proline or MeAIB.…”

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confidence: 92%

Adaptive Increase of Amino Acid Transport System A Requires ERK1/2 Activation

Franchi-Gazzola

Visigalli

Bussolati

et al. 1999

Journal of Biological Chemistry

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Amino acid starvation markedly stimulates the activity of system A, a widely distributed transport route for neutral amino acids. The involvement of MAPK (mitogen-activated protein kinase) pathways in this adaptive increase of transport activity was studied in cultured human fibroblasts. In these cells, a 3-fold stimulation of system A transport activity required a 6-h amino acidfree incubation. However, a rapid tyrosine phosphorylation of ERK (extracellular regulated kinase) 1 and 2, and JNK (Jun N-terminal kinase) 1, but not of p38, was observed after the substitution of complete medium with amino acid-free saline solution. ERK1/2 activity was 4-fold enhanced after a 15-min amino acid-free incubation and maintained at stimulated values thereafter. A transient, less evident stimulation of JNK1 activity was also detected, while the activity of p38 was not affected by amino acid deprivation. PD98059, an inhibitor of ERK1/2 activation, completely suppressed the adaptive increase of system A transport activity that, conversely, was unaffected by inhibitors of other transduction pathways, such as rapamycin and wortmannin, as well as by chronic treatment with phorbol esters. In the presence of either L-proline or 2-(methylaminoisobutyric) acid, two substrates of system A, the transport increase was prevented and no sustained stimulation of ERK1/2 was observed. To identify the stimulus that maintains MAPK activation, cell volume was monitored during amino acid-free incubation. It was found that amino acid deprivation caused a progressive cell shrinkage (30% after a 6-h starvation). If proline was added to amino acid-starved, shrunken cells, normal values of cell volume were rapidly restored. However, proline-dependent volume rescue was hampered if cells were pretreated with PD98059. It is concluded that (a) the triggering of adaptive increase of system A activity requires a prolonged activation of ERK1 and 2 and that (b) cell volume changes, caused by the depletion of intracellular amino acid pool, may underlie the activation of MAPKs.

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confidence: 92%

Adaptive Increase of Amino Acid Transport System A Requires ERK1/2 Activation

Franchi-Gazzola

Visigalli

Bussolati

et al. 1999

Journal of Biological Chemistry

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“…This corroborates and extends an earlier study in avian fibroblasts. Gazzola et al (1972) demonstrated an increase in uptake which was not affected by cyclohexamide or actinomycin D, hence concluding that neither protein synthesis nor DNA transcription was required. Interestingly, Hundal's group (Hyde et al 2001(Hyde et al , 2002 have shown a similar response to insulin in myocytes and adipocytes.…”

Section: Discussionmentioning

confidence: 86%

Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction

Jones¹,

Ashworth²,

Page³

et al. 2006

Reproduction

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Trans-placental transport of amino acids is vital for the developing fetus. Using the BeWo cell line as a placental model, we investigated the effect of restricting amino acid availability on amino acid transport system type A. BeWo cells were cultured either in amino acid-depleted (without non-essential amino acids) or control media for 1, 3, 5 or 6 h. System A function was analysed using a(methyl-amino)isobutyric acid (MeAIB) transcellular transport studies. Transporter (sodium coupled neutral amino acid transporter (SNAT1/2)) expression was analysed at mRNA and protein level by Northern and Western blotting respectively. Localisation was carried out using immunocytochemistry. MeAIB transcellular transport was significantly (P < 0.05) increased by incubation of the cells in amino acid-depleted medium for 1 h, and longer incubation times caused further increases in the rate of transfer. However, the initial response was not accompanied by an increase in SNAT2 mRNA; this occurred only after 3 h and further increased for the rest of the 6-h incubation. Similarly, it took several hours for a significant increase in SNAT2 protein expression. In contrast, relocalisation of existing SNAT2 transporters occurred within 30 min of amino acid restriction and continued throughout the 6-h incubation. When the cells were incubated in medium with even lower amino acid levels (without non-essential plus 0.5 3 essential amino acids), SNAT2 mRNA levels showed further significant (P < 0.0001) up-regulation. However, incubation of cells in depleted medium for 6 h caused a significant (P 5 0.014) decrease in the expression of SNAT1 mRNA. System L type amino acid transporter 2 (LAT2) expression was not changed by amino acid restriction, indicating that the responses seen in the system A transporters were not a general cell response. These data have shown that placental cells adapt in vitro to nutritional stress and have identified the physiological, biochemical and genomic mechanisms involved. Reproduction (2006) 131 951-960

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“…The data from the two sets of experiments were combined in Table II. These amino acids were chosen because they are representative of groups of amino acids that are transported by three separate and distinct amino acid transport systems in the Ehrlich's ascites tumor cell (25,26) and chick embryo heart cell (27).…”

Section: Resultsmentioning

confidence: 99%