Hypochlorite oxidation causes cross-linking of Lp(a).
When purified low density lipoprotein (LDL) or lipoprotein(a) (Lp[a]) was oxidized in vitro using concentrations of hypochlorite (50-500 microM) which might be achieved by activated neutrophils in vivo, high molecular weight species were observed on SDS polyacrylamide gels. The reaction was concentration-, temperature- and time-dependent. The high molecular weight apoprotein complexes were resistant to heating in SDS and DTT, suggesting covalent, but non-disulfide bond, cross-linking. Negligible amounts of lower molecular weight degradation products were formed. Bityrosine formation, measured by fluorescence and HPLC analysis, was found to increase with the amount of hypochlorite added. However, the molar concentration of bityrosine could not account for cross-linking, even if it was assumed that every bityrosine was intermolecular. Hypochlorite-oxidized Lp(a) and LDL were both effective as ligands for loading mouse peritoneal macrophages in vitro. We conclude that hypochlorite produced in inflammatory reactions might be important in the generation of atherogenic forms of lipoproteins.
O'Connell
A M
AM
Heart Research Institute, Camperdown, NSW, Sydney, Australia.
Gieseg
S P
SP
Stanley
K K
KK
D000328:Adult; D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000737:chemistry* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D010084:Oxidation-Reduction; D012973:Sodium Hypochlorite / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D014443:Tyrosine; C007543:dityrosine; D012973:Sodium Hypochlorite