Amino acid transport in pig lymphocytes Enhanced activity of transport system asc following mitogenic stimulation

Borghetti, Angelo F.; Tramacere, Mariarosaria; Ghiringhelli, P. D.; Severini, Alberto; Kay, John E.

doi:10.1016/0005-2736(81)90328-x

Cited by 29 publications

(8 citation statements)

References 20 publications

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“…This is the first study that directly measures the expression of ASCT1 and ASCT2 on human T cells. Concerning expression of ASCT1 and ASCT2, our results are in good agreement with previous studies, which found that the potential of resting T cells to take up Cys was very low and that it increased significantly following T cell activation141524. Concerning expression of x c − on T cells, conflicting results have been reported.…”

Section: Discussionsupporting

confidence: 89%

Activated human CD4+ T cells express transporters for both cysteine and cystine

Levring

Hansen

Nielsen

et al. 2012

Sci Rep

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Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine. Naïve T cells express no or very low levels of both cystine and cysteine transporters. However, we found that these transporters become strongly up-regulated during T cell activation and provide activated T cells with the required amount of cystine/cysteine needed for T cell proliferation. Thus, T cells are equipped with mechanisms that allow T cell activation and proliferation independently of cysteine generated by antigen presenting cells.

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Section: Discussionsupporting

confidence: 89%

Activated human CD4+ T cells express transporters for both cysteine and cystine

Levring

Hansen

Nielsen

et al. 2012

Sci Rep

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“…The enhancement of the activity of the ASC system was first characterized in pig peripheral lymphocytes following stimulation with PHA (Borghetti et al, 1979(Borghetti et al, , 1981. We have confirmed the enhancement of this activity in mouse spleen lymphocytes following stimulation with LPS or Con A.…”

Section: Discussionsupporting

confidence: 58%

“…An important factor considered in this study was the fact that mitogenic activations of lymphocytes enhance some amino acid transport activities. Recent reports have shown that in pig peripheral lymphocytes the activity of the transport system ASC increases following their stimulation with Phaseolus vulgaris agglutinin (PHA) (Borghetti et al, 1979(Borghetti et al, , 1981. It has been recognized that cysteine transport is mostly mediated by the ASC system in a variety of cells (Kilberg et al, 1979;Hayashi et al, 1980).…”

mentioning

confidence: 99%

Regulation of glutathione levels in mouse spleen lymphocytes by transport of cysteine

Ishii

Sugita

Bannai

1987

Journal Cellular Physiology

146

102

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Cysteine and cystine transport activities of resting and activated mouse spleen lymphocytes were characterized in order to examine the contributions of cysteine and cystine to intracellular glutathione contents. Following stimulation with lipopolysaccharide, the lymphocytes markedly increased their capacity to transport cysteine. The uptake of cysteine was mediated mainly by the ASC system (Na+-dependent neutral amino acid transport system especially reactive with alanine, serine, and cysteine). On the other hand, both the resting and the activated lymphocytes had extremely low cystine transport activities. Because of the instability of cysteine, the culture media usually contained cystine but not cysteine. Therefore, both the resting and the activated lymphocytes rapidly decreased their glutathione contents owing to their poor capacities to take up cystine. The effects of freshly added cysteine on the cellular glutathione contents were examined in the presence of bathocuproinedisulfonate, a nontoxic copper-specific chelator that inhibits autoxidation of cysteine. Cysteine added at 25-400 microM only partially prevented the rapid decrease of the glutathione contents in fresh resting lymphocytes. In the lipopolysaccharide-activated cells, however, cysteine enhanced the cellular glutathione contents in a dose-dependent manner. These results indicate that the enhanced activity of the ASC system increases the level of intracellular glutathione in the presence of cysteine.

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“…4B) internal glutamate (in sodium phosphate buffer, no potassium present). Under these conditions, the presence of substrate inside facilitates the exchange of radiolabel across the membrane by a process known as trans-stimulation (Borghetti et al, 1981). In this experiment, in which the potassium-dependent reorientation of the carrier cannot occur, we observed no differences between the amount of substrate exchanged in the presence or absence of 1 U/ml Parawixin1.…”

Section: Dose-response Curve For the Parawixin1 Stimulation Of L-[mentioning

confidence: 60%

Enhancing Glutamate Transport: Mechanism of Action of Parawixin1, a Neuroprotective Compound from Parawixia bistriata Spider Venom

Fontana

Beleboni²,

Wojewodzic³

et al. 2007

Mol Pharmacol

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Previous studies have shown that a compound purified from the spider Parawixia bistriata venom stimulates the activity of glial glutamate transporters and can protect retinal tissue from ischemic damage. To understand the mechanism by which this compound enhances transport, we examined its effects on the functional properties of glutamate transporters after solubilization and reconstitution in liposomes and in transfected COS-7 cells. Here, we demonstrate in both systems that Parawixin1 promotes a direct and selective enhancement of glutamate influx by the EAAT2 transporter subtype through a mechanism that does not alter the apparent affinities for the cosubstrates glutamate or sodium. In liposomes, we observed maximal enhancement by Parawixin1 when extracellular sodium and intracellular potassium concentrations are within physiological ranges. Moreover, the compound does not enhance the reverse transport of glutamate under ionic conditions that favor efflux, when extracellular potassium is elevated and the sodium gradient is reduced, nor does it alter the exchange of glutamate in the absence of internal potassium. These observations suggest that Parawixin1 facilitates the reorientation of the potassiumbound transporter, the rate-limiting step in the transport cycle, a conclusion further supported by experiments showing that Parawixin1 does not stimulate uptake by an EAAT2 transport mutant (E405D) defective in the potassium-dependent reorientation step. Thus, Parawixin1 enhances transport through a novel mechanism targeting a step in the transport cycle distinct from substrate influx or efflux and provides a basis for the design of new drugs that act allosterically on transporters to increase glutamate clearance.

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Amino acid transport in pig lymphocytes Enhanced activity of transport system asc following mitogenic stimulation

Cited by 29 publications

References 20 publications

Activated human CD4+ T cells express transporters for both cysteine and cystine

Activated human CD4+ T cells express transporters for both cysteine and cystine

Regulation of glutathione levels in mouse spleen lymphocytes by transport of cysteine

Enhancing Glutamate Transport: Mechanism of Action of Parawixin1, a Neuroprotective Compound from Parawixia bistriata Spider Venom

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