Hydrogen peroxide triggers an increase in cell surface expression of system xc- in cultured human glioma cells.

Abstract:
:System xc- exchanges extracellular cystine for intracellular glutamate across the plasma membrane of many cell types. One of the physiological roles of System xc- is to provide cystine for synthesis of the antioxidant glutathione. Here we report that hydrogen peroxide (H2O2) triggers the translocation of System xc- to the plasma membrane within 10 min of the initial exposure. Specifically, we observed a three-fold increase in 35S-l-cystine uptake following a 10 min exposure to 0.3 mM H2O2. This effect was dose-dependent with an EC50 for H2O2 of 65 μM. We then used cell surface biotinylation analysis to test the hypothesis that the increase in activity is due to an increased number of transporters on the plasma membrane. We demonstrated that the amount of transporter protein, xCT, localized to the plasma membrane doubles within 10 min of H2O2 exposure as a result of an increase in its delivery rate and a reduction in its internalization rate. In addition, we demonstrated that H2O2 triggered a rapid decrease in total cellular glutathione which recovered within 2 h of the oxidative insult. The kinetics of glutathione recovery matched the time course for the recovery of xCT cell surface expression and System xc- activity following removal of the oxidative insult. Collectively, these results suggest that oxidants acutely modulate the activity of System xc- by increasing its cell surface expression, and that this process may serve as an important mechanism to increase de novo glutathione synthesis during periods of oxidative stress.
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NEUROCHEMISTRY INTERNATIONAL
NEUROCHEM INT
最新影响因子:4.297 | 期刊ISSN:0197-0186 | CiteScore:3.68 |
出版周期:Monthly | 是否OA:YES | 出版年份:1980 |
期刊官方网址:http://www.journals.elsevier.com/neurochemistry-international/
期刊投稿地址:http://ees.elsevier.com/nci/
自引率:2.60% | 研究方向:医学-神经科学 |
出版地区:ENGLAND |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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《神经化学国际》致力于神经化学领域优秀原创文章的快速出版和及时评论。将审议范围广泛的主题手稿,包括分子和细胞神经化学、神经药理学和中枢神经功能的遗传方面、神经免疫学、代谢以及中枢神经和精神疾病的神经化学。
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1 |
大类(学科):Neuroscience
小类(学科):Cellular and Molecular Neuroscience
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#26/85
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2 |
大类(学科):Biochemistry, Genetics and Molecular Biology
小类(学科):Cell Biology
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#87/264
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