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Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells

OBJECTIVE: Dimethyl fumarate (DMF) is an anti-inflammatory and antioxidant drug used to treat multiple sclerosis, but its mechanism(s) of action are not fully understood. In central nervous system (CNS) cells, DMF activates nuclear factor E2-related factor 2 (Nrf2), perhaps ameliorating oxidative st...

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Autores principales: Fiedler, Sarah E., Kerns, Amelia R., Tsang, Catherine, Love, Haley N., Salinthone, Sonemany
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669026/
https://www.ncbi.nlm.nih.gov/pubmed/29096692
http://dx.doi.org/10.1186/s13104-017-2862-8
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author Fiedler, Sarah E.
Kerns, Amelia R.
Tsang, Catherine
Love, Haley N.
Salinthone, Sonemany
author_facet Fiedler, Sarah E.
Kerns, Amelia R.
Tsang, Catherine
Love, Haley N.
Salinthone, Sonemany
author_sort Fiedler, Sarah E.
collection PubMed
description OBJECTIVE: Dimethyl fumarate (DMF) is an anti-inflammatory and antioxidant drug used to treat multiple sclerosis, but its mechanism(s) of action are not fully understood. In central nervous system (CNS) cells, DMF activates nuclear factor E2-related factor 2 (Nrf2), perhaps ameliorating oxidative stress-induced damage. However, it is not known whether DMF also activates Nrf2 in peripheral immune cells, which are known to participate in CNS demyelination. We conducted a single observation study to determine whether DMF can activate Nrf2 in peripheral immune cells in vitro. RESULTS: We performed enzyme-linked immunosorbent assays to measure Nrf2 activation in nuclear extracts of human peripheral blood mononuclear cells treated with DMF at time points from 0 to 6 h, initially determining that DMF did not activate Nrf2, and that the mechanism(s) of action of DMF may thus differ in the periphery compared to the CNS. However, further analyses of our data suggest that high T(max) variability is masking Nrf2 activation in individual donors. Additionally, there may be sub-populations of responders, perhaps related to genetic polymorphisms in Nrf2. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-017-2862-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-56690262017-11-15 Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells Fiedler, Sarah E. Kerns, Amelia R. Tsang, Catherine Love, Haley N. Salinthone, Sonemany BMC Res Notes Research Note OBJECTIVE: Dimethyl fumarate (DMF) is an anti-inflammatory and antioxidant drug used to treat multiple sclerosis, but its mechanism(s) of action are not fully understood. In central nervous system (CNS) cells, DMF activates nuclear factor E2-related factor 2 (Nrf2), perhaps ameliorating oxidative stress-induced damage. However, it is not known whether DMF also activates Nrf2 in peripheral immune cells, which are known to participate in CNS demyelination. We conducted a single observation study to determine whether DMF can activate Nrf2 in peripheral immune cells in vitro. RESULTS: We performed enzyme-linked immunosorbent assays to measure Nrf2 activation in nuclear extracts of human peripheral blood mononuclear cells treated with DMF at time points from 0 to 6 h, initially determining that DMF did not activate Nrf2, and that the mechanism(s) of action of DMF may thus differ in the periphery compared to the CNS. However, further analyses of our data suggest that high T(max) variability is masking Nrf2 activation in individual donors. Additionally, there may be sub-populations of responders, perhaps related to genetic polymorphisms in Nrf2. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-017-2862-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-02 /pmc/articles/PMC5669026/ /pubmed/29096692 http://dx.doi.org/10.1186/s13104-017-2862-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Note
Fiedler, Sarah E.
Kerns, Amelia R.
Tsang, Catherine
Love, Haley N.
Salinthone, Sonemany
Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells
title Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells
title_full Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells
title_fullStr Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells
title_full_unstemmed Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells
title_short Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells
title_sort donor variability may mask dimethyl fumarate’s effects on nuclear factor e2-related factor 2 in human peripheral blood mononuclear cells
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669026/
https://www.ncbi.nlm.nih.gov/pubmed/29096692
http://dx.doi.org/10.1186/s13104-017-2862-8
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