Am J Physiol Cell Physiol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 281: C1964-C1970, 2001;
0363-6143/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (27)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rimaniol, A.-C.
Right arrow Articles by Gras, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rimaniol, A.-C.
Right arrow Articles by Gras, G.
Vol. 281, Issue 6, C1964-C1970, December 2001

Role of glutamate transporters in the regulation of glutathione levels in human macrophages

Anne-Cécile Rimaniol1, Patricia Mialocq1, Pascal Clayette1,2, Dominique Dormont1, and Gabriel Gras1

1 Service de Neurovirologie, CEA, DSV/DRM, Centre de Recherches du Service de Santé des Armées, Ecole Pratique des Hautes Etudes, Institut Paris Sud sur les Cytokines, 92265 Fontenay-aux-Roses cedex; and 2 Société de Pharmacologie et d'Immunologie-BIO, 91741 Massy, France

Cysteine is the limiting precursor for glutathione synthesis. Because of its low bioavailability, cysteine is generally produced from cystine, which may be taken up through two different transporters. The cystine/glutamate antiporter (x<UP><SUB>C</SUB><SUP>−</SUP></UP> system) transports extracellular cystine in exchange for intracellular glutamate. The XAG transport system takes up extracellular cystine, glutamate, and aspartate. Both are sensitive to competition between cystine and glutamate, and excess extracellular glutamate thus inhibits glutathione synthesis, a nonexcitotoxic mechanism for glutamate toxicity. We demonstrated previously that human macrophages express the glutamate transporters excitatory amino acid transporter (EAAT)1 and EAAT2 (which do not transport cystine, X<UP><SUB>AG</SUB><SUP>−</SUP></UP> system) and overcome competition for the use of cystine transporters. We now show that macrophages take up cystine through the x<UP><SUB>C</SUB><SUP>−</SUP></UP> and not the XAG system. We also found that glutamate, although competing with cystine uptake, dose-dependently increases glutathione synthesis. We used inhibitors to demonstrate that this increase is mediated by EAATs. EAAT expression in macrophages thus leads to glutamate-dependent enhancement of glutathione synthesis by providing intracellular glutamate for direct insertion in glutathione and also for fueling the intracellular pool of glutamate and trans-stimulating the cystine/glutamate antiporter.

cystine; glutamate/cystine antiporter; oxidative stress; glutamine


This article has been cited by other articles:


Home page
 JCOHome page
T. Dragovich, M. Gordon, D. Mendelson, L. Wong, M. Modiano, H.-H. S. Chow, B. Samulitis, S. O'Day, K. Grenier, E. Hersh, et al.
Phase I Trial of Imexon in Patients With Advanced Malignancy
J. Clin. Oncol., May 1, 2007; 25(13): 1779 - 1784.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. Ehrchen, L. Steinmuller, K. Barczyk, K. Tenbrock, W. Nacken, M. Eisenacher, U. Nordhues, C. Sorg, C. Sunderkotter, and J. Roth
Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes
Blood, February 1, 2007; 109(3): 1265 - 1274.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
G. Gras, F. Porcheray, B. Samah, and C. Leone
The glutamate-glutamine cycle as an inducible, protective face of macrophage activation
J. Leukoc. Biol., November 1, 2006; 80(5): 1067 - 1075.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
F. Porcheray, C. Leone, B. Samah, A.-C. Rimaniol, N. Dereuddre-Bosquet, and G. Gras
Glutamate metabolism in HIV-infected macrophages: implications for the CNS
Am J Physiol Cell Physiol, October 1, 2006; 291(4): C618 - C626.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online