Suppression of anionic amino acid transport impairs the maintenance of intracellular glutamate in Ha-ras-expressing cells.
When the expression of a Ha-ras oncogene is triggered in NIH3T3 cells, a progressive inhibition of sodium dependent transport of anionic amino acids through system X-AG is observed. After 48 h of ras expression the transport activity of system X-AG is almost abolished, while other transport systems involved in anionic amino acid transport are unaffected or even stimulated. In the presence of high extracellular concentrations of glutamine, the intracellular concentration of glutamate is comparable in ras expressing and non-expressing cells. On the contrary, when the extracellular pool of glutamine is depleted by the enzyme L-asparaginase, intracellular glutamate decreases at a much faster rate in ras expressing, low-transport cells. These results suggest that transport system X-AG significantly contributes to the homeostasis of intracellular glutamate under conditions of glutamine deprivation.
Uggeri
J
J
Istituto di Patologia Generale, Università degli Studi di Parma, Italy.
Belletti
S
S
Bussolati
O
O
Dall'Asta
V
V
Gazzola
G C
GC
D016475:3T3 Cells; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001215:Asparaginase / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis
D000596:Amino Acids; D000838:Anions; D002352:Carrier Proteins; D011994:Recombinant Proteins; D005973:Glutamine; D018698:Glutamic Acid; D003907:Dexamethasone; D001215:Asparaginase; D015689:Oncogene Protein p21(ras)