Dihydrolipoic acid as an effective cofactor for peptide methionine sulfoxide reductase in enzymatic repair of oxidative damage to both lipid-free and lipid-bound apolipoprotein a-I.
The aim of this study was to examine the possible use of dihydrolipoic acid (DHLA), the reduced form of lipoic acid, in the reduction of oxidized apolipoprotein A-I mediated by peptide methionine sulfoxide reductase (PMSR), and to test the accessibility of methionine sulfoxides in the lipid-bound oxidized apolipoprotein A-I to this reaction. We show that DHLA acts as an effective cofactor for PMSR, mediating restoration of the native secondary structure, tertiary structure, stability, and lipid-binding properties of the native unoxidized protein. Reconstituted high-density lipoproteins were used to demonstrate effective enzymatic reduction of the lipid-bound oxidized protein in the presence of DHLA. These findings suggest that the enzymatic repair of oxidative damage to intact lipoproteins could provide a model of a possible repair mechanism active in vivo during oxidative stress and that the restoration of high-density lipoprotein function could be one of the therapeutic benefits of lipoic acid.
Sigalov
Alexander B
AB
Biomedical Department, AMW Biomed, 22-1-11 Tarusskaya Street, Moscow 117588, Russia. alexsig@mit.edu
Stern
Lawrence J
LJ
D016632:Apolipoprotein A-I / Q000378:metabolism*; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*
D016632:Apolipoprotein A-I; D007202:Indicators and Reagents; D008075:Lipoproteins, HDL; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D004134:Dimyristoylphosphatidylcholine