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Myeloperoxidase-derived oxidants modify apolipoprotein A-I and generate dysfunctional HDL : comparison of hypothiocyanous acid (HOSCN) with hypochlorous acid (HOCl).
MedLine Citation:
PMID:  23088652     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Oxidative modification of high-density lipoproteins (HDL) by myeloperoxidase (MPO) compromises its anti-atherogenic properties, which may contribute to the development of atherosclerosis. Although it has been established that hypochlorous acid (HOCl) produced by MPO targets apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, the role of the other major oxidant generated by MPO, hypothiocyanous acid (HOSCN), in the generation of dysfunctional HDL has not been examined. In this study, we characterise the structural and functional modifications of lipid-free apoA-I and reconstituted, discoidal rHDL containing apoA-I complexed with phospholipid, induced by HOSCN and its decomposition product, cyanate (OCN-). Treatment of apoA-I with HOSCN resulted in oxidation of Trp residues, whereas OCN- induced carbamylation of Lys residues to yield homocitrulline. Trp residues were more readily oxidised on apoA-I contained in rHDL. Exposure of lipid-free apoA-I to HOSCN and OCN- significantly reduced the extent of cholesterol efflux from cholesterol-loaded macrophages when compared to unmodified apoA-I. In contrast, HOSCN did not affect the anti-inflammatory properties of rHDL. The ability of HOSCN to impair apoA-I mediated cholesterol efflux may contribute to the development of atherosclerosis, particularly in smokers who have high plasma levels of SCN-.
Authors:
Katrina A Hadfield; David I Pattison; Bronwyn E Brown; Liming Hou; Kerry-Anne Rye; Michael J Davies; Clare L Hawkins
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-23
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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