Haptoglobin Binding to Apolipoprotein A-I Prevents Damage from Hydroxyl Radicals on Its Stimulatory Activity of the Enzyme Lecithin-Cholesterol Acyl-Transferase
- 7 September 2007
- journal article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 46 (39), 11158-11168
- https://doi.org/10.1021/bi7006349
Abstract
Apolipoprotein A-I (ApoA-I), a major component of HDL, binds haptoglobin, a plasma protein transporting to liver or macrophages free Hb for preventing hydroxyl radical production. This work aimed to assess whether haptoglobin protects ApoA-I against this radical. Human ApoA-I structure, as analyzed by electrophoresis and MS, was found severely altered by hydroxyl radicals in vitro. Lower alteration of ApoA-I was found when HDL was oxidized in the presence of haptoglobin. ApoA-I oxidation was limited also when the complex of haptoglobin with both high-density lipoprotein and Hb, immobilized on resin beads, was exposed to hydroxyl radicals. ApoA-I function to stimulate cholesterol esterification was assayed in vitro by using ApoA-I-containing liposomes. Decreased stimulation was observed when liposomes oxidized without haptoglobin were used. Conversely, after oxidative stress in the presence of haptoglobin (0.5 microM monomer), the liposome activity did not change. Plasma of carrageenan-treated mice was analyzed by ELISA for the levels of haptoglobin and ApoA-I, and used to isolate HDL for MS analysis. Hydroxyproline-containing fragments of ApoA-I were found associated with low levels of haptoglobin (18 microM monomer), whereas they were not detected when the haptoglobin level increased (34-70 microM monomer). Therefore haptoglobin, when circulating at enhanced levels with free Hb during the acute phase of inflammation, might protect ApoA-I structure and function against hydroxyl radicals.Keywords
This publication has 17 references indexed in Scilit:
- Crystallographic Analysis of Calcium-dependent Heparin Binding to Annexin A2Published by Elsevier ,2006
- The immune response in atherosclerosis: a double-edged swordNature Reviews Immunology, 2006
- Free radicals in blood: Evolving concepts in the mechanism of ischemic heart diseaseArchives of Biochemistry and Biophysics, 2006
- Assignment of the Binding Site for Haptoglobin on Apolipoprotein A-IJournal of Biological Chemistry, 2005
- Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular diseaseJCI Insight, 2004
- Expression of Concern: Carrageenan‐induced mouse paw oedema is biphasic, age‐weight dependent and displays differential nitric oxide cyclooxygenase‐2 expressionBritish Journal of Pharmacology, 2004
- Hypochlorite-modified High Density Lipoprotein, a High Affinity Ligand to Scavenger Receptor Class B, Type I, Impairs High Density Lipoprotein-dependent Selective Lipid Uptake and Reverse Cholesterol TransportPublished by Elsevier ,2002
- Hydrogen peroxide in the human bodyFEBS Letters, 2000
- Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production.JCI Insight, 1996
- Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Are lactoferrin and transferrin promoters of hydroxyl-radical generation?Biochemical Journal, 1987