The thiol redox system in glioma biology : clinical target and significance in resistance to glioma chemotherapy

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Title: The thiol redox system in glioma biology : clinical target and significance in resistance to glioma chemotherapy
Authors: McBean, Gethin J.
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Date: Jul-2013
Abstract: Sulfur-containing compounds play an essential role in maintaining redox balance in glioma cells. Chief amongst these are the reduced and oxidised (disulfide) forms of cysteine (cysteine/cystine) and glutathione (GSH /GSSG) as well as thioredoxin and glutaredoxin, members of the thiol-disulfide oxidoreductases. GSH is also important as an antioxidant, as a ‘safe’ storage form of cysteine and for detoxification reactions involving the GSH sulfur transferase family of enzymes. Glioma cells contain a high concentration of GSH, compared to normal astrocytes, which renders these cells particularly resistant to chemotherapeutic agents. The rate of synthesis of GSH is controlled by the availability of cysteine, which is imported in its oxidised form, cystine, through specialized channels in the plasma membrane. These channels, known as the cystine-glutamate xc- exchanger, operate by taking up cystine in exchange for glutamate, which is released into the extracellular medium. Glioma cells export large quantities of glutamate by this mechanism, which, if unchecked, causes damage and eventual death of surrounding neurones. Thus, GSH synthesis in glioma cells fuels resistance to chemotherapy and, at the same time, kills off surrounding neurones thereby providing space for tumor cell growth. Much is now known of the molecular mechanism of cystine import and of GSH synthesis in glioma cells. In particular, a number of therapeutic strategies that target the cystine-glutamate exchanger have been proposed on the basis that this would inhibit synthesis of GSH and remove the source of glutamate release. This review describes new developments in the field of glioma cell redox balance and evaluates the potential for clinical intervention at the level of cysteine and GSH biosynthesis that may prove effective in combating brain tumor growth and development.
Type of material: Book Chapter
Publisher: Nova Science Publishers
Copyright (published version): 2013, Nova Publishers
Keywords: GliomaAstrocyteCysteineGSHOxidoreductasexCTCystine-glutamate exchangerTranssulfuration
Language: en
Status of Item: Peer reviewed
Is part of: Wiranowska, M. and Vrionis, F. D. (eds.). Gliomas: symptoms, diagnosis and treatment options
ISBN: 978-1-62618-106-9
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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