Disease relevance of Bityrosine

• Increases in dityrosine levels have been associated with pathologies such as eye cataracts, atherosclerosis, acute inflammation, and Alzheimer's disease [1].
• Toxicity did not correlate with the ability to form amyloid or perturb the acyl-chain region of a lipid membrane as measured by diphenyl-1,3,5-hexatriene anisotropy, but did correlate with lipid peroxidation and dityrosine formation [2].
• Dityrosine was detected in the coronary effluent of hearts infused with synthetic ONOO-. In hearts subjected to 20 min of global, no-flow ischemia there was a marked rise in endogenous ONOO- formation which peaked at 30 s of reperfusion [3].
• Plasma levels of protein-bound chlorotyrosine, NO2Tyr, dityrosine, and orthotyrosine, specific molecular fingerprints for distinct oxidative pathways upregulated in atheroma, were determined by mass spectrometry [4].
• A recombinant fragment of CUT-2, produced in E. coli, can be cross-linked in vitro by horse radish peroxidase via dityrosine formation to give large molecular species [1] [5].

High impact information on Bityrosine

• To analyze the mechanism of assembly of the fertilization membrane of the sea urchin Strongylocentrotus purpuratus, we inhibited the ovoperoxidase that catalyzes dityrosine formation to isolate an uncrosslinked, soft fertilization membrane (SFM) [6].
• As the DIT2 gene product has significant homology with cytochrome P-450s, DIT2 may be responsible for catalyzing the oxidation of tyrosine residues in the formation of dityrosine [7].
• Taking advantage of the natural fluorescence imparted to yeast spores by the presence of a dityrosine-containing macromolecule in the spore wall, we identified and cloned two genes, termed DIT1 and DIT2, which are required for spore wall maturation [7].
• We speculate that protein dityrosine cross-linking by myeloperoxidase may play a role in bacterial killing or injuring normal tissue [8].
• Activated neutrophils likewise converted polypeptide tyrosines to dityrosine [8].

Chemical compound and disease context of Bityrosine

• Site-specific nitration and oxidative dityrosine bridging of the tau protein by peroxynitrite: implications for Alzheimer's disease [9].
• Of these, five were derived from tryptophan; namely hydroxytryptophan, N-formylkynurenine, kynurenine, residues consistent with the dehydration of kynurenine, and hydroxykynurenine, while three were derived from tyrosine; namely dihydroxyphenylalanine, dityrosine, and a cross-linked residue consistent with a hydroxylated dityrosine residue [10].

Biological context of Bityrosine

• DIT2, which is a member of the cytochrome P450 superfamily, is responsible for the dimerization reaction leading to the dityrosine-containing precursors [11].
• Although homozygous tep1 mutants initiate the meiotic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the surface [12].
• Current analytical methods for the detection of dityrosine, a biomarker of oxidative stress, in biological samples [1].
• Although the proteins (peptides) of the spore wall are insoluble, the macromolecule containing dityrosine can be solubilized by partial acid hydrolysis of spore walls [13].
• Both AOPP-HSA and AGE-HSA, but not purified dityrosine, were capable of triggering the oxidative burst of human monocytes in cultures [14].

Anatomical context of Bityrosine

• At fertilization, the glycocalyx (vitelline layer) of the sea urchin egg is transformed into an elevated fertilization envelope by the association of secreted peptides and the formation of intermolecular dityrosine bonds [15].
• The requirement for H2O2 and the inhibition by heme poisons suggest that activated phagocytes synthesize dityrosine by a peroxidative mechanism [16].
• Aedes aegypti chorion peroxidase (CPO) plays a crucial role in chorion hardening by catalyzing chorion protein cross-linking through dityrosine formation [17].
• Comparable results, in terms of dityrosine release, were obtained using red blood cells of different sources after exposing them to a flux of H(2)O(2) [18].
• Ovoperoxidase, the enzyme that catalyzes the dityrosine cross-linking of fertilization membranes of eggs from the sea urchin Stronglyocentrotus purpuratus, exhibits slow changes in catalytic activity upon alterations of pH, with attendant changes in spectral properties [19].

Associations of Bityrosine with other chemical compounds

• The binding of [3H]cAMP and of 8-N3-[32P]cAMP to RI regulatory subunits was decreased. .OH caused a loss of tryptophan 260 fluorescence at site A of PKAI and of bityrosine production [20].
• We purified the oxidation products to apparent homogeneity by cation and anion exchange chromatographies and identified the compounds as dityrosine (3,3'-dityrosine), trityrosine (3,3',5',3"-trityrosine) and pulcherosine (5-[4"-(2-carboxy-2-aminoethyl)phenoxy]3, 3'-dityrosine) by high resolution NMR spectroscopy and mass spectrometry [21].
• Human phagocytes employ the myeloperoxidase-hydrogen peroxide system to synthesize dityrosine, trityrosine, pulcherosine, and isodityrosine by a tyrosyl radical-dependent pathway [21].
• Phorbol ester-stimulated human neutrophils and monocyte-derived macrophages similarly generated dityrosine from L-tyrosine by a pathway inhibited by catalase, aminotriazole, and azide [16].
• We also provide evidence that dityrosine moieties are formed during iron loading into ferritin by its own ferroxidase activity and that the dityrosine formation is dependent upon the oxidation of cysteine residues, especially cysteine 90 [22].

Gene context of Bityrosine

• The role of dityrosine formation in the crosslinking of CUT-2, the product of a second cuticlin gene of Caenorhabditis elegans [23].
• Regarding the colloidal insoluble multimerized Tg (m-Tg), which bears dityrosine bridges and is present in the follicular lumen, a mild oxidative system generated different soluble forms of Tg, more or less compacted by hydrophobic associations, and linked with Grp78 and Grp94 [24].
• Blood samples were drawn pre-HD, pre-IVIR, and post-IVIR for iron, transferrin, TNF-alpha, AOPP, thiol, total antioxidant capacity (TEAC), and dityrosine levels and pre-HD for ferritin and CRP levels [25].
• Previous studies have shown that exposure to oxidative and nitrative species stabilizes alpha-synuclein filaments in vitro, and this stabilization may be due to dityrosine cross-linking [26].
• The same conclusion was reached independently by an investigation of spores of a strain homozygous for the mutation gcn1, which lack the outermost layers of the spore wall and were practically devoid of dityrosine [27].

Analytical, diagnostic and therapeutic context of Bityrosine

• Parallel analyses of peritoneal lavage proteins for protein dityrosine and nitrotyrosine, molecular markers for oxidative modification by tyrosyl radical and (.)NO(2), respectively, revealed marked reductions in the content of nitrotyrosine, but not dityrosine, in MPO(-/-) samples [28].
• The oxidative damage has been manifested by SDS-PAGE, accumulation of carbonyl and bityrosine, as well as loss of tryptophan and protein thiols [29].
• Separation of an acid hydrolysate of Candida cell walls by reverse-phase high-performance liquid chromatography revealed a fluorescence peak that coelutes with the reagent dityrosine [30].
• Infusion of SNAP also abolished dityrosine release at reperfusion and improved the recovery of post-ischemic function [3].
• Video microscopy of whole Candida organisms revealed the characteristic dityrosine intensity maximum at pH approximately 10 and the intensity minimum at pH approximately 2 [30].

References