title: Dimethyl fumarate modulates antioxidant and lipid metabolism in oligodendrocytes.
abstract: Oxidative stress contributes to pathology associated with inflammatory brain disorders and therapies that upregulate antioxidant pathways may be neuroprotective in diseases such as multiple sclerosis. Dimethyl fumarate, a small molecule therapeutic for multiple sclerosis, activates cellular antioxidant signaling pathways and may promote myelin preservation. However, it is still unclear what mechanisms may underlie this neuroprotection and whether dimethyl fumarate affects oligodendrocyte responses to oxidative stress. Here, we examine metabolic alterations in oligodendrocytes treated with dimethyl fumarate by using a global metabolomic platform that employs both hydrophilic interaction liquid chromatography-mass spectrometry and shotgun lipidomics. Prolonged treatment of oligodendrocytes with dimethyl fumarate induces changes in citric acid cycle intermediates, glutathione, and lipids, indicating that this compound can directly impact oligodendrocyte metabolism. These metabolic alterations are also associated with protection from oxidant challenge. This study provides insight into the mechanisms by which dimethyl fumarate could preserve myelin integrity in patients with multiple sclerosis.
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, USA.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Taraboletti
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, USA; Department of Biology, University of Akron, Akron, OH 44325, USA. Electronic address: lshriver@uakron.edu.
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
mesh_terms: D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002952:Citric Acid Cycle / Q000187:drug effects; D000069462:Dimethyl Fumarate / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D055442:Metabolome / Q000187:drug effects; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D025341:Principal Component Analysis; D053719:Tandem Mass Spectrometry
chemical_list: D007166:Immunosuppressive Agents; D006861:Hydrogen Peroxide; D000069462:Dimethyl Fumarate
keywords: Hydrophilic interaction liquid chromatography; Metabolomics; Neuroprotection; Oligodendrocyte; Shotgun lipidomics