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Myeloperoxidase-Induced Oxidation of Albumin and Ceruloplasmin: Role of Tyrosines

I. I. Vlasova1,2,a*, A. V. Sokolov1,3,4, V. A. Kostevich1,3, E. V. Mikhalchik1, and V. B. Vasilyev3,4

1Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia

2I. M. Sechenov First Moscow State Medical University, Institute for Regenerative Medicine, Laboratory of Navigational Redox Lipidomics, 119991 Moscow, Russia

3Institute of Experimental Medicine, 197376 St. Petersburg, Russia

4St. Petersburg State University, 199034 St. Petersburg, Russia

* To whom correspondence should be addressed.

Received February 22, 2019; Revised March 14, 2019; Accepted March 14, 2019
Neutrophil myeloperoxidase (MPO) plays an important role in protecting the body against infections. MPO products – hypohalous acids and phenoxyl radicals – are strong oxidants that can damage not only foreign intruders but also host tissues, including blood plasma proteins. Here, we compared the MPO-induced oxidation of two plasma proteins with antioxidant properties – human serum albumin (HSA) and ceruloplasmin (CP). Incubation of both proteins with hypochlorite (NaOCl) or catalytically active MPO (MPO + H2O2), which synthesizes hypochlorous acid (HOCl) in the presence of chloride ions, resulted in the quenching of protein tryptophan fluorescence. Oxidation-induced changes in the structures of HSA and CP were different. HSA efficiently neutralized MPO-generated oxidants without protein aggregation, while CP oxidation resulted in the formation of large aggregates stabilized by strong covalent bonds between the aromatic amino acid residues. Tyrosine is present in the plasma as free amino acid and also as a component of the polypeptide chains of the proteins. The number of tyrosine residues in a protein does not determine its propensity for aggregate formation. In the case of CP, protein aggregation was primarily due to the high content of tryptophan residues in its polypeptide chain. MPO-dependent oxidation of free tyrosine results in the formation of tyrosyl radicals, that do not oxidize aromatic amino acid residues in proteins because of the high rate of recombination with dityrosine formation. At the same time, free tyrosine can influence MPO-induced protein oxidation due to its ability to modulate HOCl synthesis in the MPO active site.
KEY WORDS: hypochlorous acid, phenoxyl radicals, protein oxidation, tryptophan fluorescence, protein aggregation

DOI: 10.1134/S0006297919060087