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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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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. |
format | Online Article Text |
id | pubmed-5669026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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