Hypochlorite induces the formation of LDL−, a potentially atherogenic low density lipoprotein subspecies

[摘要]

Oxidation of low density lipoprotein (LDL) induced by hypochlorous acid (HOCl) leading to LDL⁻, a minimally oxidized subspecies of LDL, was investigated. LDL⁻ is characterized by its greater electronegativity and oxidative status, and is found in plasma in vivo. Its concentration was found to be elevated under conditions that predispose humans to atherosclerosis. We found that HOCl also converts LDL rapidly to an even more oxidized state, identified as LDL²⁻, which is more electronegative than LDL⁻. After milder oxidation for short durations, formation of LDL⁻ takes place while less LDL²⁻ is formed. Under these conditions, addition of methionine not only suppressed further oxidation of LDL but also favored the formation of LDL⁻ over LDL²⁻, possibly by removing chloramines at lysyl residues of LDL. The presence of lipoprotein-deficient plasma did not prevent HOCl-mediated conversion of LDL to more electronegative species. It is concluded that the HOCl-mediated conversion of LDL into more electronegative species might be physiologically relevant.

[学科分类] 生物化学/生物物理

[关键词] Low density lipoprotein;Hypochlorous acid;Minimally oxidized low density lipoprotein;Lipoprotein-deficient plasma;EDTA;ethylenediaminetetraacetic acid;MPO;myeloperoxidase;REM;relative electrophoretic mobility;LDL;low density lipoprotein;LDP;lipoprotein-deficient plasma