Dimethyl fumarate induces glutathione recycling by upregulation of glutathione reductase

Publication type:
Journal article
Metadata:
Autoren
  • Christina Hoffmann
  • Michael Dietrich
  • Ann-Kathrin Herrmann
  • Teresa Schacht
  • Philipp Albrecht
  • Axel Methner
Sammlungen
  • metadata
ISSN
1942-0994
Zeitschrift
Oxidative medicine and cellular longevity
Schlüsselwörter
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Paginierung
Art. 6093903
Datum der Veröffentlichung
2017
Herausgeber
Landes Bioscience
Herausgeber URL
http://dx.doi.org/10.1155/2017/6093903
Datum der Datenerfassung
2020
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Zugang
Public
Titel
Dimethyl fumarate induces glutathione recycling by upregulation of glutathione reductase
Ausgabe der Zeitschrift
2017

Data source: METADATA.UB

Other metadata sources:
Abstract
<jats:p>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<jats:italic>in vitro</jats:italic>. 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<jats:italic>E. coli</jats:italic>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.</jats:p>
Autoren
  • Christina Hoffmann
  • Michael Dietrich
  • Ann-Kathrin Herrmann
  • Teresa Schacht
  • Philipp Albrecht
  • Axel Methner
DOI
10.1155/2017/6093903
eISSN
1942-0994
ISSN
1942-0900
Zeitschrift
Oxidative Medicine and Cellular Longevity
Sprache
en
Paginierung
1 - 8
Datum der Veröffentlichung
2017
Status
Published
Herausgeber
Hindawi Limited
Herausgeber URL
http://dx.doi.org/10.1155/2017/6093903
Datum der Datenerfassung
2017
Titel
Dimethyl Fumarate Induces Glutathione Recycling by Upregulation of Glutathione Reductase
Ausgabe der Zeitschrift
2017

Data source: Crossref

Author's licence
CC-BY
Autoren
  • Christina Hoffmann
  • Michael Dietrich
  • Ann-Kathrin Herrmann
  • Teresa Schacht
  • Philipp Albrecht
  • Axel Methner
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-OA-Publizieren (2012 - 2017)
Resource version
Published version
DOI
10.1155/2017/6093903
Funding acknowledgements
  • DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin
File(s) embargoed
false
Open access
true
ISSN
1942-0994
Zeitschrift
Oxidative medicine and cellular longevity
Schlüsselwörter
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Open access status
Open Access
Paginierung
Art. 6093903
Datum der Veröffentlichung
2017
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/7449
Herausgeber
Landes Bioscience
Herausgeber URL
http://dx.doi.org/10.1155/2017/6093903
Datum der Datenerfassung
2022
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Zugang
Public
Titel
Dimethyl fumarate induces glutathione recycling by upregulation of glutathione reductase
Ausgabe der Zeitschrift
2017

Files

dimethyl_fumarate_induces_glu-20220715114558149.pdf

Data source: OPENSCIENCE.UB

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