Document Detail

Selective reduction of hydroperoxyeicosatetraenoic acids to their hydroxy derivatives by apolipoprotein-D: Implications for lipid antioxidant activity and Alzheimer's disease.
MedLine Citation:
PMID:  22150111     Owner:  NLM     Status:  Publisher    
Apolipoprotein-D (apoD) is upregulated in Alzheimer's disease (AD) and upon oxidative stress. ApoD inhibits brain lipid peroxidation in vivo but the mechanism is unknown. Specific Met residues may inhibit lipid peroxidation by reducing radical-propagating lipid hydroperoxides to non-reactive hydroxides via a reaction that generates methionine sulfoxide (MetSO). Since apoD has three conserved Met residues (M49, M93, M157), we generated recombinant proteins with either one or all Met residues replaced by Ala and assessed their capacity to reduce hydroperoxyeicosatetraenoic acids (HpETEs) to their hydroxyeicosatetraenoic acid (HETE) derivatives. ApoD, apoD(M49-A) and apoD(M157-A) all catalysed the reduction of HpETEs to their corresponding HETEs. Amino acid analysis of HpETE-treated apoD revealed a loss of one third of the Met residues accompanied by the formation of MetSO. Additional studies using apoD(M93-A) indicated M93 was required for HpETE reduction. We also assessed the impact that apoD MetSO formation has on protein aggregation by Western blotting of HpETE-treated apoD and human brain samples. ApoD Met oxidation was associated with formation of apoD aggregates that were also detected in AD hippocampus. In conclusion, conversion of HpETE to HETE is mediated by apoD M93, a process that may contribute to apoD antioxidant function.
Surabhi Bhatia; Bianca Knoch; Jenny Wong; Woojin Scott Kim; Paul L Else; Aaron J Oakley; Brett Garner
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-12
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     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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