Faculty Collaboration Database

The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein. Arch Biochem Biophys 1997 May 15;341(2):287-94

Date

05/15/1997

Pubmed ID

9169017

DOI

10.1006/abbi.1997.9975

Scopus ID

2-s2.0-0031570305 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

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, which 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 Cu2+, 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 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 an intrinsic antioxidants of LDL are discussed.

Author List

Ferguson E, Singh RJ, Hogg N, Kalyanaraman B

Authors

Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antioxidants
Apolipoprotein B-100
Apolipoproteins B
Copper
Cyclic N-Oxides
Electron Spin Resonance Spectroscopy
Kinetics
Lipid Peroxidation
Lipoproteins, LDL
Nitrates
Nitrogen Oxides
Oxidation-Reduction
Pyridines
Spin Labels
Sulfhydryl Compounds
Sulfhydryl Reagents
Vitamin E