Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment. | ||||||||
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Plasma membrane gamma-glutamyltransferase activity facilitates the uptake of vitamin C in melanoma cells.Corti A, Raggi C, Franzini M, Paolicchi A, Pompella A, Casini AF Department of Experimental Pathology B.M.I.E., University of Pisa Medical School, Via Roma 55, 56126 Pisa, Italy. Adequate cellular transport of ascorbic acid (AA) and its oxidation product dehydroascorbate (DHA) is assured through specific carriers. It was shown that vitamin C is taken up as DHA by most cell types, including cancer cells, via the facilitative GLUT transporters. Thus, AA oxidation to DHA can be considered a mechanism favoring vitamin C uptake and intracellular accumulation. We have investigated whether such an AA-oxidizing action might be provided by plasma membrane gamma-glutamyltransferase (GGT), previously shown to function as an autocrine source of prooxidants. The process was studied using two distinct human metastatic melanoma clones. It was observed that the Me665/2/60 clone, expressing high levels of membrane GGT activity, was capable of effecting the oxidation of extracellular AA, accompanied by a marked increase of intracellular AA levels. The phenomenon was not observed with Me665/2/21 cells, possessing only traces of membrane GGT. On the other hand, AA oxidation and stimulation of cellular uptake were indeed observed after transfection of 2/21 cells with cDNA coding for GGT. The mechanism of GGT-mediated AA oxidation was investigated in acellular systems, including GGT and its substrate glutathione. The process was observed in the presence of redox-active chelated iron(II) and of transferrin or ferritin, i.e., two physiological iron sources. Thus, membrane GGT activity-often expressed at high levels in human malignancies-can oxidize extracellular AA and promote its uptake efficiently. Published 5 November 2004 in Free Radic Biol Med, 37(11): 1906-15.
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