The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death.
Ana Banjac,Tamara Perisic,Hideyo Sato,Hideyo Sato,Alexander Seiler,Shiro Bannai,Norbert Weiss,Pirkko Kölle,K Tschoep,Rolf D. Issels,Peter T. Daniel,Marcus Conrad,Georg W. Bornkamm +12 more
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The results show that system xc− protects against oxidative stress not by elevating intracellular GSH levels, but rather creates a reducing extracellular environment by driving a highly efficient cystine/cysteine redox cycle, which must be viewed as a discrete major regulator of cell survival.Abstract:
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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
Journal ArticleDOI
Ferroptosis: mechanisms, biology and role in disease.
TL;DR: In this paper, the authors provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of the potential therapeutic roles, and its pathological roles, together with a potential for therapeutic targeting.
Journal ArticleDOI
Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis
Scott J. Dixon,Darpan N Patel,Matthew Welsch,Rachid Skouta,Eric D Lee,Miki Hayano,Ajit G. Thomas,Caroline E Gleason,Nicholas P. Tatonetti,Barbara S. Slusher,Brent R. Stockwell +10 more
TL;DR: Dixon, Patel, et al. as mentioned in this paper found that erastin is a very effective inhibitor of system xc− function and that it is over 1000 times more potent than the previously known best inhibitor, sulfasalazine.
Journal ArticleDOI
Mechanisms of ferroptosis
TL;DR: Outstanding questions include the relationship between ferroPTosis and other forms of cell death, and whether activation or inhibition of ferroptosis can be exploited to achieve desirable therapeutic ends.
Journal ArticleDOI
The cystine/glutamate antiporter system xc- in health and disease: From molecular mechanisms to novel therapeutic opportunities
Jan Lewerenz,Sandra J. Hewett,Ying Huang,Maria P. Lambros,Peter W. Gout,Peter W. Kalivas,Ann Massie,Ilse Julia Smolders,Axel Methner,Mathias Pergande,Sylvia B. Smith,Vadivel Ganapathy,Pamela Maher +12 more
TL;DR: By phylogenetic analysis, it is shown that system x(c)(-) is a rather evolutionarily new amino acid transport system and its diverse roles in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS are highlighted.
References
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Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues
TL;DR: The use of the foregoing analytical method in the determination of total and oxidized glutathione contents of rat blood, kidney, and liver gave values in good agreement with those obtained by previous investigators.
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Physiological functions of thioredoxin and thioredoxin reductase.
Elias S.J. Arnér,Arne Holmgren +1 more
TL;DR: All mammalian thioredoxin reduct enzyme isozymes are homologous to glutathione reductase and contain a conserved C-terminal elongation with a cysteine-selenocysteine sequence forming a redox-active selenenylsulfide/selenolthiol active site and are inhibited by goldthioglucose and other clinically used drugs.
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Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress
TL;DR: Glutamate-induced cytotoxicity in N18-RE-105 cells is due to inhibition of cystine uptake, resulting in lowered glutathione levels leading to oxidative stress and cell death.
Journal ArticleDOI
Cloning and Expression of a Plasma Membrane Cystine/Glutamate Exchange Transporter Composed of Two Distinct Proteins
TL;DR: In this paper, the authors have isolated cDNA encoding the transporter for system xc- from mouse activated macrophages by expression in Xenopus oocytes, and the sequence analysis revealed that one is identical with the heavy chain of 4F2 cell surface antigen (4F2hc) and the other is a novel protein of 502 amino acids with 12 putative transmembrane domains.