Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression

The Journal of Pharmacology and Experimental Therapeutics
Inas HelwaWendy B Bollag

Abstract

Oxidative stress contributes to inflammatory skin diseases, including psoriasis. Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular antioxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses. We used Western analysis, immunofluorescence, and real-time quantitative reverse-transcription polymerase chain reaction to examine the effect of MMF on the expression of Nrf2 and its targets. We also measured intracellular reactive oxygen species (ROS) levels following MMF treatment. Our data show that MMF increased total and nuclear Nrf2 levels in primary mouse keratinocytes and enhanced mRNA expression of several Nrf2-downstream effectors, including heme oxygenase-1 and peroxiredoxin-6. Moreover, MMF treatment attenuated the generation of ROS following hydrogen peroxide treatment. On the other hand, the expression and membranous localizatio...Continue Reading

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Citations

Apr 1, 2018·Experimental Dermatology·Jürgen BrückKamran Ghoreschi
Apr 11, 2018·Frontiers in Pharmacology·Montserrat Rojo de la VegaGeorg T Wondrak
Apr 9, 2020·American Journal of Physiology. Cell Physiology·Wendy B BollagKelly A Hyndman
Jun 8, 2021·Biochimie·Inês V da SilvaGraça Soveral
Oct 30, 2021·Pharmaceutical Biology·Lucía Yepes-Molina, Micaela Carvajal

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