Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD+ Synthesis During Inflammation and Infection.

Frontiers in Immunology
J R MoffettAryan M Namboodiri

Abstract

Quinolinate (Quin) is a classic example of a biochemical double-edged sword, acting as both essential metabolite and potent neurotoxin. Quin is an important metabolite in the kynurenine pathway of tryptophan catabolism leading to the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). As a precursor for NAD+, Quin can direct a portion of tryptophan catabolism toward replenishing cellular NAD+ levels in response to inflammation and infection. Intracellular Quin levels increase dramatically in response to immune stimulation [e.g., lipopolysaccharide (LPS) or pokeweed mitogen (PWM)] in macrophages, microglia, dendritic cells, and other cells of the immune system. NAD+ serves numerous functions including energy production, the poly ADP ribose polymerization (PARP) reaction involved in DNA repair, and the activity of various enzymes such as the NAD+-dependent deacetylases known as sirtuins. We used highly specific antibodies to protein-coupled Quin to delineate cells that accumulate Quin as a key aspect of the response to immune stimulation and infection. Here, we describe Quin staining in the brain, spleen, and liver after LPS administration to the brain or systemic PWM administration. Quin expression was strong in immun...Continue Reading

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Citations

Jul 28, 2020·Cells·José A Rodríguez-GómezMiguel A Burguillos
Mar 24, 2021·Cellular and Molecular Life Sciences : CMLS·Massimiliano GasparriniNadia Raffaelli
May 11, 2021·Frontiers in Neurology·Austin Perlmutter
Jun 8, 2021·Frontiers in Molecular Biosciences·Benjamin GrothSu-Ju Lin
Aug 1, 2021·Proceedings of the National Academy of Sciences of the United States of America·Libia Alejandra García-FloresJohn R Speakman
Aug 27, 2021·Metabolites·Se-Ran JunMartin Hauer-Jensen

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Methods Mentioned

BETA
electrophoresis
nuclear translocation

Software Mentioned

MASCOT
DeCyder

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