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Title:
The oxidative stress-inducible cystine/glutamate antiporter, system x c β : cystine supplier and beyond | Amino Acids
Description:
The oxidative stress-inducible cystine/glutamate exchange system, system x c β , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x c β has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x c β may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x c β research up to now.
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google, scholar, pubmed, cas, article, bannai, cell, biol, cystine, sato, amino, cells, glutamate, redox, chem, system, glutathione, cancer, transport, cystineglutamate, transporter, cysteine, human, acids, oxidative, mouse, xct, physiol, role, acid, extracellular, membrane, activity, expression, nat, induction, biophys, ishii, biochem, tamba, antiporter, conrad, stress, issue, macrophages, growth, res, transporters, research, exchange,
Topics {βοΈ}
pathogen-induced interleukin-1beta processing month download article/chapter cystine-glutamate transporter slc7a11 xcβ cystine/glutamate antiporter cystine/glutamate transporter-deficient mice endotoxin-induced lung injury glutamate/cystine antiporter system oxidative stress-inducible genes bleomycin-induced lung fibrosis cystine-glutamate transporter xcβ cystine/glutamate exchange transporter glutamate-induced oxidative stress caveolin-1/beta-catenin pathway cystine/glutamate transporter gene 4f2 heavy chain small-cell lung cancer glutamate-induced cytotoxic processes cystine-cysteine shuttle mediated herpesvirus fusion-entry receptor oxidized low-density lipoprotein bid-mediated mitochondrial damage aif-dependent cell death dfg-priority programme spp1190 marcus conrad οΏ½οΏ½ cystine/glutamate antiporter aif-mediated cell death thiol redox state gsh-independent redox system cystine/cysteine cycle allele-specific antioxidant activity membrane redox state potential redox regulation full article pdf cystine transporter xct s-nitroso-l-cysteine human cystine transporter article conrad cystine/glutamate transporter cystine-transporter gene author information authors potential therapeutic target review article published biphasic redox response xct-deficient cells amino acid transporter privacy choices/manage cookies xct-deficient mice neuronal glutathione deficiency amino acid response falk mh
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- Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
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headline:The oxidative stress-inducible cystine/glutamate antiporter, system x c β : cystine supplier and beyond
description:The oxidative stress-inducible cystine/glutamate exchange system, system x
c
β
, transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x
c
β
has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x
c
β
may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x
c
β
research up to now.
datePublished:2011-03-16T00:00:00Z
dateModified:2011-03-16T00:00:00Z
pageStart:231
pageEnd:246
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Cystine/cysteine redox cycle
Glutamate
Glutathione
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xCT
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Life Sciences
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headline:The oxidative stress-inducible cystine/glutamate antiporter, system x c β : cystine supplier and beyond
description:The oxidative stress-inducible cystine/glutamate exchange system, system x
c
β
, transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x
c
β
has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x
c
β
may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x
c
β
research up to now.
datePublished:2011-03-16T00:00:00Z
dateModified:2011-03-16T00:00:00Z
pageStart:231
pageEnd:246
sameAs:https://doi.org/10.1007/s00726-011-0867-5
keywords:
4F2
Cystine/cysteine redox cycle
Glutamate
Glutathione
Slc7a11
xCT
Biochemistry
general
Analytical Chemistry
Biochemical Engineering
Life Sciences
Proteomics
Neurobiology
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