Uptake of glutamate and cysteine in C-6 glioma cells and in cultured astrocytes.
The uptake of glutamate in rat glioma C-6 cells and cultured astrocytes derived from rat cerebral hemispheres was found to be mediated by a Na(+)-dependent and a Na(+)-independent system. The Na(+)-dependent system was inhibited by aspartate and was consistent with the commonly occurring system designated system X-AG. The Na(+)-independent system was inhibited by cystine and was consistent with system x-c described in various types of cells in the periphery. It was also found that quisqualate selectively and competitively interfered with the Na(+)-independent glutamate uptake. In C-6 cells, the glutamate uptake via systems X-AG and x-c accounted for approximately 35% and 55% of the total uptake, respectively, at 0.05 mM glutamate. In cultured astrocytes, the glutamate uptake via system X-AG was very potent, whereas the uptake via system xc- was relatively weak and its contribution to the total uptake of glutamate seemed almost negligible. However, in both C-6 cells and astrocytes, system xc- was necessary for the uptake of cystine, another substrate of system xc-. Cystine in the culture medium was an essential precursor of glutathione, and the inhibition of the cystine uptake by excess glutamate as a competitor led to a severe deficiency in glutathione, followed by cell degeneration.
Cho
Y
Y
Department of Biochemistry, Tsukuba University Medical School, Ibaraki, Japan.
Bannai
S
S
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D003553:Cystine / Q000493:pharmacokinetics*; D018691:Excitatory Amino Acid Antagonists; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D005971:Glutamates / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D012964:Sodium / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D003553:Cystine; D012964:Sodium; D005978:Glutathione