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Title

A novel approach to enhancing cellular glutathione levels

AuthorsMaher, Pamela; Lewerenz, Jan; Lozano, Carles; Torres, Josep Lluís
KeywordsOxidative stress
Cysteine
Cystine
Cysteamine
Epicatechin
Issue Date12-Aug-2008
PublisherBlackwell Publishing
CitationJournal of Neurochemistry 107(3): 690–700 (2008)
AbstractGlutathione (GSH) and GSH-associated metabolism provide the major line of defense for the protection of cells from oxidative and other forms of toxic stress. Of the three amino acids that comprise GSH, cysteine is limiting for GSH synthesis. Since extracellularly cysteine is readily oxidized to form cystine, cystine transport mechanisms are essential to provide cells with cysteine. Cystine uptake is mediated by system xc−, a Na+-independent cystine/glutamate antiporter. Inhibition of system xc− by millimolar concentrations of glutamate, a pathway termed oxidative glutamate toxicity, results in GSH depletion and nerve cell death. Recently, we described a series of compounds derived from the conjugation of epicatechin with cysteine and cysteine derivatives that protected nerve cells in culture from oxidative glutamate toxicity by maintaining GSH levels. In this paper, we characterize an additional epicatechin conjugate, cysteamine-epicatechin, that is 5-10 fold more potent than the earlier conjugates. In addition, we show that these epicatechin conjugates maintain GSH levels by enhancing the uptake of cystine into cells through induction of a disulfide exchange reaction, thereby uncoupling the uptake from system xc−. Thus, these novel epicatechin conjugates have the potential to enhance GSH synthesis under a wide variety of forms of toxic stress.
Description20 pages, 9 figures, 1 table.-- PMID: 18702664 [PubMed].-- PMCID: PMC2644427.-- NIHMSID: NIHMS90383.-- Printed version published Nov 2008.
Publisher version (URL)http://dx.doi.org/10.1111/j.1471-4159.2008.05620.x
URIhttp://hdl.handle.net/10261/25341
DOI10.1111/j.1471-4159.2008.05620.x
ISSN0022-3042
E-ISSN1471-4159
Appears in Collections:(IQAC) Artículos
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