Enzymatic repair of oxidative damage to human apolipoprotein A‐I

FEBS Letters

Stern, Lawrence J.¹  Sigalov, Alexander B.² 

[1] Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA;Biomedical Department, AMW Co. Ltd., 22-1-11 Tarusskaya Street, Moscow 117588, Russia

关键词: Apolipoprotein A-I;    Methionine oxidation;    Enzymatic reduction;    Peptide methionine sulfoxide reductase;    HDL;    high density lipoproteins;    apo A-I;    apolipoprotein A-I;    PMSR;    peptide methionine sulfoxide reductase;    DTT;    dithiothreitol;    DHPC;    1;    2-diheptanoyl-sn-glycero-3-phosphocholine;    CMC;    critical micellar concentration;    apo A-Iunox;    unoxidized apo A-I contained in initial serum apo A-I;    apo A-IOX;    oxidized apo A-I contained in serum apo A-I or obtained from unoxidized apo A-I using hydrogen peroxide;    apo A-Ired;    reduced apo A-I obtained by reduction of oxidized apo A-I using PMSR;    DHPC;    1;    2-diheptanoyl-sn-glycero-3-phosphocholine;    POPC;    1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine;    DMPC;    1;    2-dimyristoyl-sn-glycero-3-phosphocholine;   

DOI  :  10.1016/S0014-5793(98)00908-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Oxidative damage to apolipoprotein A-I that occurs in vivo commonly involves methionine oxidation, and is accompanied by alterations in structure, lipid association, and cholesterol efflux function. We have used the enzyme peptide methionine sulfoxide reductase (PMSR) to reverse this damage, and shown by a variety of criteria that enzyme treatment restores the primary, secondary, and tertiary structure and lipid association characteristic of the native unoxidized protein. Lipid-associated as well as lipid-free apolipoprotein A-I reacts with PMSR, suggesting that enzymatic reduction of oxidized apolipoprotein A-I in high density lipoproteins can result in restoration of biological activity and the ability to promote cholesterol efflux from cells.

【 授权许可】

Unknown