Iron as a catalyst of human low-density lipoprotein oxidation: Critical factors involved in its oxidant properties

被引:2
作者
Lapenna, Domenico
Ciofani, Giuliano
Obletter, Gabriele
机构
[1] Univ G DAnnunzio, Dipartimento Med & Sci Invecchiamento, Ctr Excellence Aging, Ctr Sci Invecchiamento & Med Traslaz CeSI MeT, I-66100 Chieti, Italy
[2] Univ G DAnnunzio, Lab Fisiopatol Stress Ossidat, Ctr Excellence Aging, Ctr Sci Invecchiamento & Med Traslaz CeSI MeT, I-66100 Chieti, Italy
关键词
Iron; LDL oxidation; Antioxidants; Acidic pH; Lipid hydroperoxides; Atherosclerosis; Lysosomes; ION-DEPENDENT OXIDATION; LIPID-PEROXIDATION; METAL-ION; GLUTATHIONE-PEROXIDASE; ALPHA-TOCOPHEROL; MECHANISMS; HYDROPEROXIDES; LOCALIZATION; HEPATOCYTES; ASSOCIATION;
D O I
10.1016/j.jtemb.2017.02.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Iron-induced human LDL oxidation, which is relevant to atherosclerosis, has not yet been properly investigated. We addressed such issue using iron(II) and (III) basically in the presence of phosphates, which are present in vivo and influence iron oxidative properties, at pH 4.5 and 7.4, representative, respectively, of the lysosomal and plasma environment. In 10 mM phosphate buffered saline (PBS), iron(II) induces substantial LDL oxidation at pH 4.5 at low micromolar concentrations, while at pH 7.4 has low oxidative effects; iron(III) promotes small LDL oxidation only at pH 4.5. In 10 mM sodium acetate/NaCl buffer, pH 4.5, iron-induced LDL oxidation is far higher than in PBS, highlighting the relevance of phosphates in the inhibitory modulation of iron-induced LDL oxidation. LDL oxidation is related to iron binding to the protein and lipid moiety of LDL, and requires the presence of iron(II) bound to LDL together with iron(III). Chemical modification of LDL carboxyl groups, which could bind iron especially at pH 4.5, decreases significantly iron binding to LDL and iron-induced LDL oxidation. Hydroxyl radical scavengers are ineffective on iron-induced LDL oxidation, which is inhibited by metal chelation, scavengers of alkoxyl/peroxyl radicals, or removal of LDL lipid hydroperoxides (LOOH). Overall, substantial human LDL oxidation is induced LOOH-dependently by iron(II) at pH 4.5 even in the presence of phosphates, suggesting the occurrence of iron(II)-induced LDL oxidation in vivo within lysosomes, where pH is about 4.5, iron(II) and phosphates coexist, plasma with its antioxidants is absent, and glutathione peroxidase is poorly expressed resulting in LOOH accumulation. (C) 2017 Elsevier GmbH. All rights reserved.
引用
收藏
页码:111 / 118
页数:8
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