Dimethyl Itaconate Is Not Metabolized into Itaconate Intracellularly
Open accessAbstract
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 [ 13 C]itaconate and dimethyl [ 13 C]itaconate (DMI) to probe itaconate metabolism, and find that [ 13 C]DMI is not metabolized to itaconate. [ 13 C]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.
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IRG1 plays a major role in embryo implantation in the womb.
“it also appears to play a major role in embryo implantation in the womb, a process thought to require immunosuppression70–72.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [71]
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References 17 · Cited by 125
- Authors
- ElAzzouny, M., Tom, C. T. M. B., Evans, C. R., Olson, L. L., Tanga, M. J., Gallagher, K. A., Martin, B. R., & Burant, C. F.
- Affiliations
- University of Michigan (US)
- SRI International (US)
- Corresponding author
- ElAzzouny, Mahmoud
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 292
- Issue
- 12
- Pages
- 4766-4769
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC5377792
- OpenAlex
- W2587237321
- Cited by
- 125
- References
- 17
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 19 · 2023: 14 · 2022: 21 · 2021: 10 · 2020: 16 · 2019: 6 · 2018: 8 · 2017: 1
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (P30DK089503, P30DK020572, U24DK097153, DP2GM114848, F31EB019320, K08DK102357)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- itaconate, dimethyl itaconate, cellular uptake, succinic acid, macrophages, lipopolysaccharide stimulation, carbon isotope labeling
- MeSH terms
- RAW 264.7 Cells, Animals, Cells, Cultured, Inflammation, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Succinates, Succinic Acid, Mice, Metabolomics, Metabolome
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