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Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase
Joint Authors
Hoffmann, Christina
Dietrich, Michael
Herrmann, Ann-Kathrin
Schacht, Teresa
Albrecht, Philipp
Methner, Axel
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-01-01
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Neuronal degeneration in multiple sclerosis has been linked to oxidative stress.
Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis.
DMF activates the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) leading to increased synthesis of the major cellular antioxidant glutathione (GSH) and prominent neuroprotection in vitro.
We previously demonstrated that DMF is capable of raising GSH levels even when glutathione synthesis is inhibited, suggesting enhanced GSH recycling.
Here, we found that DMF indeed induces glutathione reductase (GSR), a homodimeric flavoprotein that catalyzes GSSG reduction to GSH by using NADPH as a reducing cofactor.
Knockdown of GSR using a pool of E.
coli RNase III-digested siRNAs or pharmacological inhibition of GSR, however, also induced the antioxidant response rendering it impossible to verify the suspected attenuation of DMF-mediated neuroprotection.
However, in cystine-free medium, where GSH synthesis is abolished, pharmacological inhibition of GSR drastically reduced the effect of DMF on glutathione recycling.
We conclude that DMF increases glutathione recycling through induction of glutathione reductase.
American Psychological Association (APA)
Hoffmann, Christina& Dietrich, Michael& Herrmann, Ann-Kathrin& Schacht, Teresa& Albrecht, Philipp& Methner, Axel. 2017. Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-8.
https://search.emarefa.net/detail/BIM-1195160
Modern Language Association (MLA)
Hoffmann, Christina…[et al.]. Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-8.
https://search.emarefa.net/detail/BIM-1195160
American Medical Association (AMA)
Hoffmann, Christina& Dietrich, Michael& Herrmann, Ann-Kathrin& Schacht, Teresa& Albrecht, Philipp& Methner, Axel. Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-8.
https://search.emarefa.net/detail/BIM-1195160
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195160