Selective Resistance of LDL Core Lipids to Iron-Mediated Oxidation
| Autor: | Elaine L. Gong, Berbie M. Chu, Ronald M. Krauss, Diane L. Tribble, Gerri A. Levine |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Iron
Macrophages Oxidative phosphorylation Conjugated system medicine.disease_cause Porphyrin Lipoproteins LDL Lipid peroxidation chemistry.chemical_compound chemistry Biochemistry LDL receptor Cholesteryl ester medicine Humans Lipid Peroxidation Cardiology and Cardiovascular Medicine Oxidative stress Hemin |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 16:1580-1587 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Although the nature and consequences of oxidative changes in the chemical constituents of low density lipoproteins (LDLs) have been extensively examined, the physical dynamics of LDL oxidation and the influence of physical organization on the biological effects of oxidized LDLs have remained relatively unexplored. To address these issues, in the present studies we monitored surface- and core-specific peroxidative stress relative to temporal changes in conjugated dienes (CDs), particle charge (an index of oxidative protein modification), and LDL-macrophage interactions. Peroxidative stress in LDL surface and core compartments was evaluated with the site-specific, oxidation-labile fluorescent probes parinaric acid (PnA) and PnA cholesteryl ester (PnCE), respectively. When oxidation was initiated by Cu 2+ , oxidative loss of the core probe (PnCE) closely followed that of the surface probe (PnA), as indicated by the time to 50% probe depletion (t 1/2 ; 15.5±7.8 and 30.4±12 minutes for PnA and PnCE, respectively). Both probes were more resistant in LDL exposed to Fe 3+ (t 1/2 , 53.2±8.1 and 346.7±155.4 minutes), although core probe resistance was much greater with this oxidant (PnCE t 1/2 /PnA t 1/2, 5.8 vs 2.0 for Cu 2+ ). Despite differences in the rate and extent of oxidative changes in Cu 2+ - versus Fe 3+ -exposed LDLs, PnCE loss occurred in close correspondence with CD formation and appeared to precede changes in particle charge under both conditions. Exposure of LDLs to hemin, a lipophilic Fe 3+ -containing porphyrin that becomes incorporated into the LDL particle, resulted in rapid loss of PnCE and simultaneous changes in particle charge, even at concentrations that yielded increases in CDs and thiobarbituric acid–reactive substances similar to those obtained with free Fe 3+ . These results suggest that oxidation of the LDL hydrophobic core occurs in conjunction with accelerated formation of CDs and may be essential for LDL protein modification. In accordance with the known effects of oxidative protein modifications on LDL receptor recognition, exposure of LDLs to Cu 2+ and hemin but not Fe 3+ produced particles that were readily processed by macrophages. Thus, the physical site of oxidative injury appears to be a critical determinant of the chemical and biological properties of LDLs, particularly when oxidized by Fe 3+ . |
| Databáze: | OpenAIRE |
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