Itaconic Acid Is a Mammalian Metabolite Induced during Macrophage Activation
2011; American Chemical Society; Volume: 133; Issue: 41 Linguagem: Inglês
10.1021/ja2070889
ISSN1943-2984
AutoresCheryl L. Strelko, Wenyun Lu, Fay J. Dufort, Thomas N. Seyfried, Thomas C. Chiles, Joshua D. Rabinowitz, Mary F. Roberts,
Tópico(s)Immune cells in cancer
ResumoItaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and 13C-labeling, we have detected ITA in both macrophage-like VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased ITA production and secretion. Crude cell extracts synthesize ITA via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.
Referência(s)