The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein

Eric Ferguson, Ravinder Jit Singh, Neil Hogg, B. Kalyanaraman

Research output: Contribution to journalArticle

21 Citations (Scopus)

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, β-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. Bath apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu2+ -mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-α- phenylnitrone (PBN) but not by the water-soluble spin trap α-(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 apoB 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 apoB thiols as intrinsic antioxidants of LDL are discussed.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume341
Issue number2
DOIs
StatePublished - May 15 1997

Fingerprint

Apolipoprotein B-100
LDL Lipoproteins
Sulfhydryl Compounds
Oxidation
Peroxynitrous Acid
Antioxidants
Apolipoproteins B
Vitamin E
Oxides
Lipids
Electron Spin Resonance Spectroscopy
Carotenoids
Baths
Lipid Peroxidation
Paramagnetic resonance
Atherosclerosis
Molecular Weight
Molecular weight
Water

Keywords

  • electron spin resonance
  • lipid peroxidation
  • low-density lipoprotein
  • peroxynitrite
  • protein thiols

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein. / Ferguson, Eric; Singh, Ravinder Jit; Hogg, Neil; Kalyanaraman, B.

In: Archives of Biochemistry and Biophysics, Vol. 341, No. 2, 15.05.1997, p. 287-294.

Research output: Contribution to journalArticle

@article{b9455a890a62483ea6fc23e8df9747d6,
title = "The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein",
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, β-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. Bath apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu2+ -mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-α- phenylnitrone (PBN) but not by the water-soluble spin trap α-(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 apoB 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 apoB thiols as intrinsic antioxidants of LDL are discussed.",
keywords = "electron spin resonance, lipid peroxidation, low-density lipoprotein, peroxynitrite, protein thiols",
author = "Eric Ferguson and Singh, {Ravinder Jit} and Neil Hogg and B. Kalyanaraman",
year = "1997",
month = "5",
day = "15",
doi = "10.1006/abbi.1997.9975",
language = "English (US)",
volume = "341",
pages = "287--294",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein

AU - Ferguson, Eric

AU - Singh, Ravinder Jit

AU - Hogg, Neil

AU - Kalyanaraman, B.

PY - 1997/5/15

Y1 - 1997/5/15

N2 - 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, β-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. Bath apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu2+ -mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-α- phenylnitrone (PBN) but not by the water-soluble spin trap α-(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 apoB 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 apoB thiols as intrinsic antioxidants of LDL are discussed.

AB - 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, β-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. Bath apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu2+ -mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-α- phenylnitrone (PBN) but not by the water-soluble spin trap α-(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 apoB 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 apoB thiols as intrinsic antioxidants of LDL are discussed.

KW - electron spin resonance

KW - lipid peroxidation

KW - low-density lipoprotein

KW - peroxynitrite

KW - protein thiols

UR - http://www.scopus.com/inward/record.url?scp=0031570305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031570305&partnerID=8YFLogxK

U2 - 10.1006/abbi.1997.9975

DO - 10.1006/abbi.1997.9975

M3 - Article

C2 - 9169017

AN - SCOPUS:0031570305

VL - 341

SP - 287

EP - 294

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -