Dityrosine is a protein oxidation product that is formed by intermolecular cross-linking of two tyrosyl radicals generated from the interaction between reactive oxygen species (ROS) and tyrosine.1,2 Intragastric administration of dityrosine (320 μg/kg per day) decreases hippocampal expression of the NMDA receptor subunits Nr1, Nr2a, and Nr2b and induces memory impairments in a novel object recognition test in mice.2 It increases fasting blood glucose levels and decreases plasma insulin levels and pancreatic expression of the insulin synthesis-related genes Ins2, Pdx1, and MafA in mice.3 Increased levels of dityrosine are positively correlated with various diseases, including autism spectrum disorder, cataracts, Alzheimer's disease, Parkinson's disease, atherosclerosis, and cystic fibrosis.4,5
|1. AmadÒ, R., Aeschbach, R., and Neukom, H. Dityrosine: In vitro production and characterization. Methods Enzymol. 107, 377-388 (1984).|2. Ran, Y., Yan, B., Li, Z., et al. Dityrosine administration induces novel object recognition deficits in young adulthood mice. Physiol. Behav. 164(Pt A), 292-299 (2016).|3. Ding, Y.Y., Li, Z.Q., Cheng, X.R., et al. Dityrosine administration induces dysfunction of insulin secretion accompanied by diminished thyroid hormones T3 function in pancreas of mice. Amino Acids 49(8), 1401-1414 (2017).|4. Anwar, A., Abruzzo, P.M., Pasha, S., et al. Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism - a source of biomarkers for clinical diagnosis. Mol. Autism 9, 3 (2018).|5. DiMarco, T., and Giulivi, C. Current analytical methods for the detection of dityrosine, a biomarker of oxidative stress, in biological samples. Mass Spectrom. Rev. 26(1), 108-120 (2007).