Regulation of amino acid transport in chick embryo heart cells II. Adaptive control sites for the “A mediation”

“…In the past we have described this phenomenon in a variety of cells [5] and tentatively attributed it to the amino acid starvation-induced de novo syn thesis of transport proteins that identifies the derepression phase of an adaptive nutri tional response [15,29], The repression phase of this regulatory response, induced by amino acid refeeding, brought the activity of the system back to the basal value [15]. In an attempt to correlate the effects of extracellu lar osmolarity and of amino acid availability on the activity of transport system A we have measured the volume of the cells incubated in normosmolar salt solutions under condi tions of amino acid starvation and refeeding.…”

Section: Discussionmentioning

confidence: 99%

Role of Amino Acid Transport System A in the Control of Cell Volume in Cultured Human Fibroblasts

Gazzola

DallˈAsta²,

Nucci

et al. 1991

Cell Physiol Biochem

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Human fibroblasts shrink and are unable to recover their initial volume when incubated in hypertonic saline solutions, whereas an efficient volume restoration takes place in hypertonic media containing substrates of the highly concentrative transport system A (amino acids and methylamines). Amino acid substrates of barely concentrative transport systems are ineffective in sustaining the volume recovery. The activity of system A increases following incubation of fibroblasts under conditions promoting cell shrinkage and decreases upon cell swelling. These results stress the role of system A in the regulation of cell volume. Adaptive changes in the activity of system A are also induced by cell starvation and refeeding (adaptive regulation). Cell starvation is associated with cell shrinkage, while cell refeeding is accompanied by cell swelling. It is suggested that nutritional regulation and cell volume control by system A may be part of a common regulatory network.

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“…This increase has been shown to be inhibited by cycloheximide and actinomycin D (9)(10)(11)(12)(13)15). In general, amino acids that are transported through the A system have been shown to be the most effective in the repression of this system (12).…”

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confidence: 99%

“…However, this specificity has been disputed (13). When derepressed cells are given an A system amino acid, a rapid decline in A system activity occurs (9)(10)(11)(12)(13). With some cell lines, a portion of this decline in activity is sensitive to cycloheximide and actinomycin D (10).…”

mentioning

confidence: 99%

Recessive constitutive mutant Chinese hamster ovary cells (CHO-K1) with an altered A system for amino acid transport and the mechanism of gene regulation of the A system.

Moffett¹,

Englesberg²

1984

Mol. Cell. Biol.

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Chinese hamster ovary cells (CHO-Kl) starved for 24 h for amino acids show a severalfold increase in velocity of proline transport through the A system (Vmax is five times that of unstarved cells). This increase is inhibited by cycloheximide, actinomycin D, N-methyl-a.-amino isobutyric acid (MeAIB, a nonmetabolizable specific A system amino acid analog), and by other amino acids that are generally transported by the A system. However, transport by the A system is not a prerequisite for this repression, and all compounds that have affinity for the A system do not necessarily act as "co-repressors." The addition of proline, MeAIB, or other amino acids, as described above, to derepressed cells results in a rapid decrease in A system activity. As shown with proline and MeAIB, this decrease in activity is in part due to a rapid transinhibition and a slow, irreversible inactivation of the A system. Neither process is inhibited by cycloheximide or actinomycin D. Alanine antagonizes the growth of CHO-Kl pro-cells by preventing proline transport, and alanine-resistant mutants (alar have been isolated (Moffett et al., Somatic Cell Genet. 9:189-213, 1983). alar2 and alar4 are partial and full constitutive mutants for the A system and have two and six times the Vmax for proline uptake by the A system, respectively. The A system in alar4 is also immune to the co-repressor-induced inactivation. Both alar2 and alar4 phenotypes are recessive. Alar3 shows an increase in Vmax and Km for proline transport through the A system, and this phenotype is codominant. All three mutants have a pleiotropic effect, producing increases in activity of the ASC and P systems of amino acid transport. This increase is not due to an increase in the Na+ gradient. The ASC and P phenotypes behave similarly to the A system in hybrids. A model has been proposed incorporating these results.The A system of amino acid transport is Na+ dependent and transports mainly the small, polar, straight-chain amino acids such as alanine, the non-metabolizable analogs 2-aminoisobutyric acid and N-methyl-oa-amino isobutyric acid (MeAIB), and also proline. This system is ubiquitous among the vertebrates (6,14,22,26,28; see references in 2, 3, and 12). Of the three Na+-dependent transport systems (A, ASC, and P) present in Chinese hamster ovary cells, CHO-Kl, the cell line with which we will be concerned, the A system, appears to be the only one whose activity is repressible (20).When cells are placed under conditions in which they are starved for amino acids, a severalfold increase in velocity (Vmax) of transport of amino acids through the A system occurs. This increase has been shown to be inhibited by cycloheximide and actinomycin D (9-13, 15). In general, amino acids that are transported through the A system have been shown to be the most effective in the repression of this system (12). However, this specificity has been disputed (13). When derepressed cells are given an A system amino acid, a rapid decline in A system activity occurs (9-13). With some cell lines, a ...

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Regulation of amino acid transport in chick embryo heart cells II. Adaptive control sites for the “A mediation”

Cited by 57 publications

References 20 publications

Proceedings of the Physiological Society, 18–19 January 1974, St.Thomas's Hospital Meeting: Communications

Proceedings of the Physiological Society, 18–19 January 1974, St.Thomas's Hospital Meeting: Communications

Role of Amino Acid Transport System A in the Control of Cell Volume in Cultured Human Fibroblasts

Recessive constitutive mutant Chinese hamster ovary cells (CHO-K1) with an altered A system for amino acid transport and the mechanism of gene regulation of the A system.

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