Oxidation of low-density lipoprotein (LDL) is recognized to be a key step in atherogenesis. Previous studies show that LDL contains low molecular weight antioxidants such as vitamin E, beta-carotene, and ubiquinol, that can retard oxidative modification. In this report, we have evaluated the antioxidant potential of apolipoprotein B-100 (apo-B) thiols during LDL oxidation. Both apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu(2+)-mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-alpha-phenylnitrone (PBN) but not by the water-soluble spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Blocking apo-B thiols with sulfhydryl modifying agents increased the oxidizability of LDL. As with Cu(2+), peroxynitrite also caused depletion of apo-B thiols, and again thiol depletion was inhibited by PBN but not by POBN. A PBN-lipid-derived radical adduct was observed by the electron spin resonance (ESR) technique during oxidation of LDL with peroxynitrite. We conclude that apo-B thiol depletion is mediated by lipid peroxidation, prior to the onset of the propagation phase of LDL oxidation. The implications of apo-B thiols as intrinsic antioxidants of LDL are discussed. ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001008-26
Application #
6448037
Study Section
Project Start
2001-03-01
Project End
2002-02-28
Budget Start
Budget End
Support Year
26
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
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