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
Mao, Li; Liu, Yu-Xiang; Huang, Chun-Hua et al. (2015) Intrinsic Chemiluminescence Generation during Advanced Oxidation of Persistent Halogenated Aromatic Carcinogens. Environ Sci Technol 49:7940-7
Shan, Guo-Qiang; Yu, Ao; Zhao, Chuan-Fang et al. (2015) A combined experimental and computational investigation on the unusual molecular mechanism of the Lossen rearrangement reaction activated by carcinogenic halogenated quinones. J Org Chem 80:180-9
Li, Yan; Huang, Chun-Hua; Liu, Yu-Xiang et al. (2014) Detoxifying polyhalogenated catechols through a copper-chelating agent by forming stable and redox-inactive hydrogen-bonded complexes with an unusual perpendicular structure. Chemistry 20:13028-33
Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang et al. (2013) Ofloxacin induces apoptosis via ?1 integrin-EGFR-Rac1-Nox2 pathway in microencapsulated chondrocytes. Toxicol Appl Pharmacol 267:74-87
Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang et al. (2013) Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression. Toxicol Appl Pharmacol 267:88-94
Shao, Jie; Huang, Chun-Hua; Kalyanaraman, Balaraman et al. (2013) Potent methyl oxidation of 5-methyl-2'-deoxycytidine by halogenated quinoid carcinogens and hydrogen peroxide via a metal-independent mechanism. Free Radic Biol Med 60:177-82
Sheng, Zhi-Guo; Li, Yan; Fan, Rui-Mei et al. (2013) Lethal synergism between organic and inorganic wood preservatives via formation of an unusual lipophilic ternary complex. Toxicol Appl Pharmacol 266:335-44
Qin, Hao; Huang, Chun-Hua; Mao, Li et al. (2013) Molecular mechanism of metal-independent decomposition of lipid hydroperoxide 13-HPODE by halogenated quinoid carcinogens. Free Radic Biol Med 63:459-66
Huang, Chun-Hua; Shan, Guo-Qiang; Mao, Li et al. (2013) The first purification and unequivocal characterization of the radical form of the carbon-centered quinone ketoxy radical adduct. Chem Commun (Camb) 49:6436-8
Liddle, Brendan J; Wanniarachchi, Sarath; Hewage, Jeewantha S et al. (2012) Electronic communication across diamagnetic metal bridges: a homoleptic gallium(III) complex of a redox-active diarylamido-based ligand and its oxidized derivatives. Inorg Chem 51:12720-8

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