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Regulation of System xc- by Pharmacological Manipulation of Cellular Thiols
Joint Authors
Albano, Rebecca
Raddatz, Nicholas J.
Hjelmhaug, Julie
Baker, David A.
Lobner, Doug
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-04-09
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
The cystine/glutamate exchanger (system xc-) mediates the transport of cystine into the cell in exchange for glutamate.
By releasing glutamate, system xc- can potentially cause excitotoxicity.
However, through providing cystine to the cell, it regulates the levels of cellular glutathione (GSH), the main endogenous intracellular antioxidant, and may protect cells against oxidative stress.
We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L-BSO), and diethyl maleate (DEM).
Both compounds caused significant concentration and time dependent decreases in intracellular GSH levels.
However; DEM caused an increase in radiolabeled cystine uptake through system xc-, while unexpectedly BSO caused a decrease in uptake.
The compounds caused similar low levels of neurotoxicity, while only BSO caused an increase in oxidative stress.
The mechanism of GSH depletion by these two compounds is different, DEM directly conjugates to GSH, while BSO inhibits γ-glutamylcysteine synthetase, a key enzyme in GSH synthesis.
As would be expected from these mechanisms of action, DEM caused a decrease in intracellular cysteine, while BSO increased cysteine levels.
The results suggest that negative feedback by intracellular cysteine is an important regulator of system xc- in this culture system.
American Psychological Association (APA)
Albano, Rebecca& Raddatz, Nicholas J.& Hjelmhaug, Julie& Baker, David A.& Lobner, Doug. 2015. Regulation of System xc- by Pharmacological Manipulation of Cellular Thiols. Oxidative Medicine and Cellular Longevity،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1075576
Modern Language Association (MLA)
Albano, Rebecca…[et al.]. Regulation of System xc- by Pharmacological Manipulation of Cellular Thiols. Oxidative Medicine and Cellular Longevity No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1075576
American Medical Association (AMA)
Albano, Rebecca& Raddatz, Nicholas J.& Hjelmhaug, Julie& Baker, David A.& Lobner, Doug. Regulation of System xc- by Pharmacological Manipulation of Cellular Thiols. Oxidative Medicine and Cellular Longevity. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1075576
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1075576