Elevation of the serotonin-derived quinone, tryptamine-4,5-dione, in the intestine of ICR mice with dextran sulfate-induced colitis

Abstract

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders associated with oxidative stress. The intestines produce 5-hydroxytryptamine that may negatively affect disease state under inflammatory conditions when overproduced. 5-Hydroxytryptamine is a substrate for myeloperoxidase and is converted into reactive tryptamine-4,5-dione. Here, an experimental colitis model was established through oral administration of 5% dextran sulfate sodium to ICR mice for 7 days. Furthermore, the formation of tryptamine-4,5-dione in the colorectal mucosa/submucosa and colorectal tissue was analyzed by chemical and immunochemical methodologies. First, free tryptamine-4,5-dione in the homogenate was chemically trapped by o -phenylenediamine and analyzed as the stable phenazine derivative. Tryptamine-4,5-dione localization as adducted proteins in the colorectal tissue was immunohistochemically confirmed, and as demonstrated by both methods, this resulted in the significant increase of tryptamine-4,5-dione in dextran sulfate sodium-challenged mice compared with control mice. Immunohistochemical staining confirmed tryptamine-4,5-dione-positive staining at the myeloperoxidase accumulation site in dextran sulfate sodium-challenged mice colorectal tissue. The tryptamine-4,5-dione locus in the mice was partly matched with that of a specific marker for myeloperoxidase, halogenated tyrosine. Overall, the results possibly indicate that tryptamine-4,5-dione is generated by neutrophil myeloperoxidase in inflammatory tissue and may contribute to the development of inflammatory bowel disease.

Covalent adduction of serotonin-derived quinones to the SARS-CoV-2 main protease expressed in a cultured cell

“…This could be due to the hydrophobicity of the side chains of vitamin K molecules. Our group has been focused on TD and Q5HIAA as endogenous serotonin-derived quinones [ 10 , 11 , 14 , 15 , 18 ] for years. COVID-19 is often accompanied by severe inflammation; therefore, myeloperoxidase could oxidize serotonin to TD when infected.…”

“…The plasmid (pLEX307) containing the sequence for the SARS-CoV-2 main protease was transfected into HEK293 cells cultured on a poly- l -lysine-coated 6-well plate using Lipofectamine® 3000 as per the manufacturer's protocol and a previously described method [ 18 ]. After 6 h of transfection in Opti-MEM, 2 mL of Dulbecco's modified Eagle medium containing 10% fetal bovine serum (FBS-DMEM) was added and further incubated for 42 h. The well was first washed with serum-free DMEM, and then quinone (final concentration of 50 μM in DMEM) was added.…”

“…In general, quinones often trigger signaling pathways as reported [ 16 ]. TD was previously found in the brain [ 17 ], atherosclerotic plaque [ 10 ], and the inflamed colon [ 18 ]. These results suggest that if TD is generated, it may have some functionality in vivo .…”