P-254 - Mechanistic view of iodide in oxidative stress

Abstract

Iodide (I-) is an important substrate used in the biosynthesis of thyroid hormones, thyroxine and triiodothyronine by thyroid peroxidase. I- is also a favoured substrate for other peroxidases that catalyze conversion of H2O2 to hypohalous acids (HOX, X=Cl, Br, I, SCN) that are important in pathogen killing. HOX can also induce host tissue damage, with this linked to multiple pathologies. Here we have analyzed the reactions of oxidized forms of I- with amino acids, peptides and proteins to determine whether I- protects against, or enhances damage induced by HOX or sensitized and direct photo-oxidation. Kinetic data were obtained using stopped-flow, competition kinetics and time-resolved photolysis. Products were analyzed by chromatography, mass spectrometry, western blot, ELISA and gel electrophoresis. Enzymatic activity was also examined. Oxidation of lysozyme by HOX or photosensitizers induces dimer formation, but also fragmentation and oxidation of Tyr, Trp, Met, Cys and His side chains. Low levels of I- provide protection against oxidation and dimer formation, but also induces specific modifications, including iodo-tyrosine and iodo-histidine. These data indicate that small increases in I- concentration may be positive, but that high levels of I- may induce alternative damage.