title: Dimethyl Itaconate Is Not Metabolized into Itaconate Intracellularly.
abstract: Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used [13C]itaconate and dimethyl [13C]itaconate (DMI) to probe itaconate metabolism, and find that [13C]DMI is not metabolized to itaconate. [13C]Itaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this study is to encourage the development of effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: ElAzzouny
authors.affiliation: Chemistry, and.
authors.forename: Christopher T M B
authors.initials: CT
authors.lastname: Tom
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Evans
authors.affiliation: SRI International, Menlo Park, California 94025.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Olson
authors.affiliation: SRI International, Menlo Park, California 94025.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Tanga
authors.affiliation: Surgery, University of Michigan, Ann Arbor, Michigan 48105 and.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Gallagher
authors.affiliation: Chemistry, and.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Martin
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Burant
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D000067996:RAW 264.7 Cells; D013386:Succinates / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D013386:Succinates; C518953:dimethyl itaconate; D019802:Succinic Acid; C005229:itaconic acid
keywords: dimethyl-itaconate; inflammation; isotopic tracer; itaconic acid; macrophage; mass spectrometry (MS); metabolomics