INTRACELLULAR THIOL TARGETS OF CHLORINATED OXIDANTS

The neutrophil oxidative burst during inflammation is a main source of oxidants in vivo. As a result of neutrophil activation, the inflammatory oxidants produced include H2O2 and chlorinated oxidants (HOCl and chloramines). These oxidants have been linked to endothelial dysfunction, a key component of various inflammatory diseases such as cancer, atherosclerosis and obesity. The relevance of chloramines to inflammatory disease is an area of great interest. Some chloramines have been shown to traverse membranes and are cytotoxic, reacting with a number of cell components, with particular preference for Cys and Met residues. Understanding which cellular targets are preferentially oxidised by chloramines could provide important clues as to how endothelial dysfunction might be mediated in the context of inflammation. The aim of this thesis was to explore the cellular thiol targets HOCl and cell-permeable chloramines (glycine chloramine, GlyCl; and monochloramine, NH2Cl) in an endothelial cell model. Specifically, the focus was to investigate each oxidant‘s effects on cells grown in culture, with treatment exposure kept to a minimum in order to specifically identify early protein thiol modifications which coul