D-Dopachrome tautomerase is an enzyme related by amino acid sequence and catalytic activity to macrophage migration inhibitory factor. Both of these small molecules are pro-inflammatory cytokines mediating broad innate immune responses. Although it is well established that the gene product of D-dopachrome tautomerase is widely expressed in liver and kidney cells, no study has mapped the distribution pattern of this tautomeric enzyme in the mammalian nervous system. Here, we address this void by characterizing the cellular localization of D-dopachrome tautomerase in the adult mouse brain. Two well-characterized polyclonal antibodies were used for Western blotting and immunohistochemical localization of the endogenous tautomeric enzyme. Our results show that D-dopachrome tautomerase is present throughout the brain parenchyma with a large fraction of heterogeneous interneurons harboring a stable and robust expression of the enzyme. These data point to a potential involvement of D-dopachrome tautomerase activity in the mature mouse brain, and suggest some functional and evolutionary relationship between innate immunity and tautomerization of D-dopachrome in mammalian species.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuroscience.2012.09.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Conformational Flexibility of the C-Terminal Region Influences Distal Active Site Residues Across the Tautomerase Superfamily.
Int J Mol Sci
November 2024
Department of Chemistry, University of the Pacific, Stockton, CA 95211, USA.
Consisting of more than 11,000 members distributed over five families, the tautomerase superfamily (TSF) is a large collection of proteins with diverse biological functions. While much attention has been given to individual TSF enzymes, a majority remain structurally and functionally uncharacterized. Given its large size, studying a representative member of each family offers a viable approach for extracting mechanistic insights applicable to the entire superfamily.
View Article and Find Full Text PDFSerum and urinary levels of MIF, CD74, DDT and CXCR4 among patients with type 1 diabetes mellitus, type 2 diabetes and healthy individuals: Implications for further research.
Metabol Open
December 2024
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Background: Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine with pleiotropic properties, mainly pro-inflammatory. MIF seems to exert its pro-inflammatory features by binding to its transmembrane cellular receptor CD74. MIF also has CXCR4, which acts as a co-receptor in this inflammatory process.
View Article and Find Full Text PDFPrognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.
Oncotarget
July 2024
School of Medicine, Yale University, New Haven, CT 06520, USA.
Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited. This retrospective study analyzed 97 patients treated at Yale for melanoma between 2002-2020.
View Article and Find Full Text PDFThe synthesis of 1,2,3-triazoles as binders of D-dopachrome tautomerase (D-DT) for the development of dual-targeting inhibitors.
Eur J Med Chem
October 2024
Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV, Groningen, the Netherlands. Electronic address:
Despite recent advances in the treatment of cancer, the issue of therapy resistance remains one of the most significant challenges in the field. In this context, signaling molecules, such as cytokines have emerged as promising targets for drug discovery. Examples of cytokines include macrophage migration inhibitory factor (MIF) and its closely related analogue D-dopachrome tautomerase (D-DT).
View Article and Find Full Text PDFMacrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities.
Int J Mol Sci
April 2024
School of Medicine, Yale University, 333 Cedar St., New Haven, CT 06510, USA.
Discovered as inflammatory cytokines, MIF and DDT exhibit widespread expression and have emerged as critical mediators in the response to infection, inflammation, and more recently, in cancer. In this comprehensive review, we provide details on their structures, binding partners, regulatory mechanisms, and roles in cancer. We also elaborate on their significant impact in driving tumorigenesis across various cancer types, supported by extensive in vitro, in vivo, bioinformatic, and clinical studies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!