The Emerging Role of 3-Hydroxyanthranilic Acid on C. elegans Aging Immune Function.

Autor:	Espejo LS; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., DeNicola D; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Chang LM; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Hofschneider V; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Haskins AE; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Balsa J; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Freitas SS; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Antenor A; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Hamming S; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Hull B; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Castro-Portuguez R; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Dang H; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA., Sutphin GL; Molecular & Cellular Biology, University of Arizona, Tucson, AZ, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 09. Date of Electronic Publication: 2024 Jan 09.
DOI:	10.1101/2024.01.07.574394
Abstrakt:	3-hydroxyanthranilic acid (3HAA) is considered to be a fleeting metabolic intermediate along tryptophan catabolism through the kynurenine pathway. 3HAA and the rest of the kynurenine pathway have been linked to immune response in mammals yet whether it is detrimental or advantageous is a point of contention. Recently we have shown that accumulation of this metabolite, either through supplementation or prevention of its degradation, extends healthy lifespan in C. elegans and mice, while the mechanism remained unknown. Utilizing C. elegans as a model we investigate how 3HAA and haao-1 inhibition impact the host and the potential pathogens. What we find is that 3HAA improves host immune function with aging and serves as an antimicrobial against gram-negative bacteria. Regulation of 3HAA's antimicrobial activity is accomplished via tissue separation. 3HAA is synthesized in the C. elegans hypodermal tissue, localized to the site of pathogen interaction within the gut granules, and degraded in the neuronal cells. This tissue separation creates a new possible function for 3HAA that may give insight to a larger evolutionarily conserved function within the immune response.
Databáze:	MEDLINE
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