Comparison of low-density lipoprotein modification by myeloperoxidase-derived hypochlorous and hypobromous acids

Myeloperoxidase (MPO). a heme enzyme secreted by activated phagocytes, cata lyzes the oxidation of halides to hypohalous acids. At plasma concentration s of halides, hypochlorous acid (HOCl) is the major strong oxidant produced . In contrast, the related enzyme eosinophil peroxidase preferentially gene rates hypobromous acid (HOBr). Since reagent and MPO-derived HOCl converts low-density lipoprotein (LDL) to a potentially atherogenic form, we investi gated the effects of HOBr on LDL modification. Compared to HOCl, HOBr cause d 2-3-fold greater oxidation of tryptophan and cysteine residues of the pro tein moiety (apoB) of LDL and 4-fold greater formation of fatty acid halohy drins from the lipids in LDL. In contrast, HOBr was 2-fold less reactive th an HOCl with lysine residues and caused little formation of N-bromamines. N evertheless. HOBr caused an equivalent increase in the relative electrophor etic mobility of LDL as HOCl, which was not reversed upon subsequent incuba tion with ascorbate, in contrast to the shift in mobility caused by HOCl. S imilar apoB modifications were observed with HOBr generated by MPO/H2O2/Br. In the presence of equivalent concentrations of Cl- and Br-, modifications of LDL by MPO resembled those seen in the presence of Br- alone. Interesti ngly, even at physiological concentrations of the two halides (100 mM Cl-. 100 muM Br), MPG utilized a portion of the Br- to oxidize apoB cysteine res idues. MPG also utilized the pseudohalide thiocyanate to oxidize apoB cyste ine residues. Our data show that even though HOBr has different reactivitie s than HOCl with apoB, it is able to alter the charge of LDL, converting it into a potentially atherogenic particle. (C) 2001 Elsevier Science Inc.