Plasma membrane γ-glutamyltransferase activity facilitates the uptake of vitamin C in melanoma cells

Alessandro Corti, Chiara Raggi, Maria Franzini, Aldo Paolicchi, Alfonso Pompella, Alessandro F. Casini

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 γ-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.

Original languageEnglish
Pages (from-to)1906-1915
Number of pages10
JournalFree Radical Biology and Medicine
Volume37
Issue number11
DOIs
Publication statusPublished - Dec 1 2004

Fingerprint

Cell membranes
Ascorbic Acid
Melanoma
Cell Membrane
Oxidation
Membranes
Iron
Clone Cells
Transferrin
Ferritins
Oxidation-Reduction
Transfection
Glutathione
Neoplasms
Complementary DNA
Cells
Substrates

Keywords

  • Dehydroascorbate
  • Free radicals
  • Melanoma cells
  • Membrane γ-glutamyltranserase
  • Vitamin C oxidation

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Plasma membrane γ-glutamyltransferase activity facilitates the uptake of vitamin C in melanoma cells. / Corti, Alessandro; Raggi, Chiara; Franzini, Maria; Paolicchi, Aldo; Pompella, Alfonso; Casini, Alessandro F.

In: Free Radical Biology and Medicine, Vol. 37, No. 11, 01.12.2004, p. 1906-1915.

Research output: Contribution to journalArticle

Corti, Alessandro ; Raggi, Chiara ; Franzini, Maria ; Paolicchi, Aldo ; Pompella, Alfonso ; Casini, Alessandro F. / Plasma membrane γ-glutamyltransferase activity facilitates the uptake of vitamin C in melanoma cells. In: Free Radical Biology and Medicine. 2004 ; Vol. 37, No. 11. pp. 1906-1915.
@article{4207b53893eb421d91051748e79ba7c7,
title = "Plasma membrane γ-glutamyltransferase activity facilitates the uptake of vitamin C in melanoma cells",
abstract = "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 γ-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.",
keywords = "Dehydroascorbate, Free radicals, Melanoma cells, Membrane γ-glutamyltranserase, Vitamin C oxidation",
author = "Alessandro Corti and Chiara Raggi and Maria Franzini and Aldo Paolicchi and Alfonso Pompella and Casini, {Alessandro F.}",
year = "2004",
month = "12",
day = "1",
doi = "10.1016/j.freeradbiomed.2004.08.015",
language = "English",
volume = "37",
pages = "1906--1915",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - Plasma membrane γ-glutamyltransferase activity facilitates the uptake of vitamin C in melanoma cells

AU - Corti, Alessandro

AU - Raggi, Chiara

AU - Franzini, Maria

AU - Paolicchi, Aldo

AU - Pompella, Alfonso

AU - Casini, Alessandro F.

PY - 2004/12/1

Y1 - 2004/12/1

N2 - 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 γ-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.

AB - 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 γ-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.

KW - Dehydroascorbate

KW - Free radicals

KW - Melanoma cells

KW - Membrane γ-glutamyltranserase

KW - Vitamin C oxidation

UR - http://www.scopus.com/inward/record.url?scp=7444264606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444264606&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2004.08.015

DO - 10.1016/j.freeradbiomed.2004.08.015

M3 - Article

VL - 37

SP - 1906

EP - 1915

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 11

ER -