Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generation of oxygen free radicals (OFR) via intravenous administration of xanthine plus xanthine oxidase [X + XO], to Inactin(R) anesthetized rats produced intense respiratory distress. This effect led to death of more than 90% of the animals within a 120 min observation period. Several reports documented that the two autocoids, 5-hydroxytryptamine (5-HT) and histamine (H), can induce pulmonary and bronchiolar constriction and pulmonary edema. Hence, our present studies were conducted to investigate whether antagonists of 5-HT and histamine could provide protection from the lethal toxicity of the free radicals. Pretreatment of the rats with pyrilamine and cimetidine, H1 and H2 receptor antagonists, respectively, prolonged the duration of survival, but it failed to enhance net survival rate. In contrast, pretreatment of the rats with nonspecific 5-HT antagonists, methysergide and cyproheptadine, and a selective 5-HT(2) receptor antagonist, ketanserin, markedly enhanced the survival rate to 80-90%. These observations are consistent with data showing that 5-HT levels in the systemic arterial blood doubled within 5-10 min after administration of [X + XO]. These studies support the view that OFR-mediated respiratory distress is caused predominantly by 5-hydroxytryptamine and to a lesser extent by histamine.
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PMID:Evaluation of the protective effects of histamine and 5-hydroxytryptamine receptor antagonists against the lethal toxicity induced by oxygen free radicals in rats. 1654 37

Serotonin (5-hydroxytryptamine; 5HT) is a favorable substrate for myeloperoxidase and is likely to be oxidized by this heme enzyme during inflammation. In this study, we have investigated how serotonin becomes conjugated to amino acid residues and proteins when it is oxidized by myeloperoxidase. 5HT formed three adducts with N-acetylcysteine (NAC) when it was incubated with myeloperoxidase, xanthine oxidase, and acetaldehyde. One of the adducts was identified as 5HT-NAC, and the others were conjugates of NAC and tryptamine-4,5-dione (TD). There was no evidence for coupling of oxidized serotonin to amine residues. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was exposed to 5HT with the enzymatic system or synthetic TD. Both caused a loss of thiols on GAPDH and covalent attachment of quinones derived from TD to the protein. Biotin-labeled 5HT was used instead of 5HT to confirm the conjugation of 5HT to GAPDH. It was incorporated into the GAPDH when oxidized by myeloperoxidase. Analysis of tryptic peptides of human GAPDH by liquid chromatography with mass spectrometry revealed that an adduct of TD was formed with the peptide containing Cys(152) and Cys(156). Our results indicate that myeloperoxidase can oxidize serotonin to species that form adducts with low molecular weight thiols and cysteine residues in proteins. Low molecular weight conjugates will redox cycle and fuel oxidative stress. Conjugation of serotonin to proteins will affect their function and may provide useful biomarkers of serotonin oxidation during inflammatory events.
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PMID:Myeloperoxidase catalyzes the conjugation of serotonin to thiols via free radicals and tryptamine-4,5-dione. 2300 81


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