Loss of 3-chlorotyrosine by inflammatory oxidants: implications for the use of 3-chlorotyrosine as a bio-marker in vivo

Biochemical and Biophysical Research Communications
Matthew Whiteman, Jeremy P E Spencer

Abstract

Activated neutrophils generate the potent oxidant hypochlorous acid (HOCl) from the enzyme myeloperoxidase (MPO). A proposed bio-marker for MPO-derived HOCl in vivo is 3-chlorotyrosine, elevated levels of which have been measured in several human inflammatory pathologies. However, it is unlikely that HOCl is produced as the sole oxidant at sites of chronic inflammation as other reactive species are also produced during the inflammatory response. The work presented shows that free and protein bound 3-chlorotyrosine is lost upon addition of the pro-inflammatory oxidants, HOCl, peroxynitrite, and acidified nitrite. Furthermore, incubation of 3-chlorotyrosine with activated RAW264.7 macrophages or neutrophil-like HL-60 cells resulted in significant loss of 3-chlorotyrosine. Therefore, at sites of chronic inflammation where there is concomitant ONOO(-) and HOCl formation, it is possible measurement of 3-chlorotyrosine may represent an underestimate of the true extent of tyrosine chlorination. This finding could account for some of the discrepancies reported between 3-chlorotyrosine levels in tissues in the literature.

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Citations

Jul 21, 2012·Rheumatology·Lisa K StampAnthony J Kettle
Jul 19, 2013·PloS One·Benjamin PulliJohn W Chen
Sep 30, 2014·Journal of Immunological Methods·Jörg FlemmigJürgen Arnhold
May 31, 2011·Journal of Immunological Methods·Agnieszka RobaszkiewiczMiroslaw Soszynski
Jul 23, 2013·Biochimica Et Biophysica Acta·Anthony J KettleRufus Turner
Apr 5, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Naihao LuYi-Yuan Peng
Oct 7, 2015·Annals of Biomedical Engineering·Jun ZhouLiping Tang
Jan 18, 2014·The Journal of Biological Chemistry·Ghassan J MaghzalRoland Stocker
Jun 11, 2017·Biological Chemistry·Kate Samardzic, Kenneth J Rodgers
Feb 16, 2011·Chemical Research in Toxicology·Matthew P CurtisJonathan W Neidigh

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