scholarly journals Lipoxygenase treatment render low-density lipoprotein susceptible to Cu2+-catalysed oxidation

1996 ◽  
Vol 314 (2) ◽  
pp. 577-585 ◽  
Author(s):  
Achim LASS ◽  
Jutta BELKNER ◽  
Hermann ESTERBAUER ◽  
Hartmut KÜHN
Keyword(s):  
Low Density Lipoprotein ◽  
Complex Mixture ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Oxidation Products ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Low Density ◽  
Catalysed Oxidation ◽  
Lag Period

Oxidative modification of low-density lipoprotein (LDL) has been implicated in foam-cell formation at all stages of atherosclerosis. Since transition metals and mammalian 15-lipoxygenases are capable of oxidizing LDL to its atherogenic form, a concerted action of these two catalysts in atherogenesis has been suggested. Cu2+-catalysed LDL oxidation is characterized by a kinetic lag period in which the lipophilic antioxidants are decomposed and by a complex mixture of unspecific oxidation products. We investigated the kinetics of the 15-lipoxygenase-catalysed oxygenation of LDL and found that the enzyme is capable of oxidizing LDL in the presence of the endogenous lipophilic antioxidants. In contrast with the Cu2+-catalysed reaction, no kinetic lag phase was detected. The pattern of products formed during short-term incubations was highly specific, with cholesterol-esterified (13S)-hydroperoxy-(9Z,11E)-octadecadienoic acid being the major product. However, after long-term incubations the product pattern was less specific. Preincubation with 15-lipoxygenase rendered human LDL more susceptible to Cu2+-catalysed oxidation as indicated by a dramatic shortening of the lag period. Addition of Cu2+ to lipoxygenase-treated LDL led to a steep decline in its antioxidant content and to a greatly reduced lag period. Interestingly, if normalized to a comparable hydroperoxide content, autoxidation and addition of exogenous hydroperoxy fatty acids both failed to overcome the lag period. The local peroxide concentrations in various LDL subcompartments will be discussed as a possible reason for this unexpected behaviour.

scholarly journals Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8312
Author(s):  
Takashi Obama ◽  
Hiroyuki Itabe
Keyword(s):  
Cardiovascular Diseases ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Vascular Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Foam Cell Formation ◽  
Low Density

Neutrophil extracellular traps (NETs) significantly contribute to various pathophysiological conditions, including cardiovascular diseases. NET formation in the vasculature exhibits inflammatory and thrombogenic activities on the endothelium. NETs are induced by various stimulants such as exogenous damage-associated molecular patterns (DAMPs). Oxidatively modified low-density lipoprotein (oxLDL) has been physiologically defined as a subpopulation of LDL that comprises various oxidative modifications in the protein components and oxidized lipids, which could act as DAMPs. oxLDL has been recognized as a crucial initiator and accelerator of atherosclerosis through foam cell formation by macrophages; however, recent studies have demonstrated that oxLDL stimulates neutrophils to induce NET formation and enhance NET-mediated inflammatory responses in vascular endothelial cells, thereby suggesting that oxLDL may be involved in cardiovascular diseases through neutrophil activation. As NETs comprise myeloperoxidase and proteases, they have the potential to mediate oxidative modification of LDL. This review summarizes recent updates on the analysis of NETs, their implications for cardiovascular diseases, and prospects for a possible link between NET formation and oxidative modification of lipoproteins.

scholarly journals Glucose oxidation and low-density lipoprotein-induced macrophage ceroid accumulation: possible implications for diabetic atherosclerosis

1994 ◽  
Vol 300 (1) ◽  
pp. 243-249 ◽  
Author(s):  
J V Hunt ◽  
M A Bottoms ◽  
K Clare ◽  
J T Skamarauskas ◽  
M J Mitchinson
Keyword(s):  
Glucose Concentration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protein Glycation ◽  
Ldl Oxidation ◽  
Low Density ◽  
Catalysed Oxidation ◽  
Induce Lipid Peroxidation ◽  
High Concentrations

The exposure of proteins to high concentrations of glucose in vitro is widely considered a relevant model of the functional degeneration of tissue occurring in diabetes mellitus. In particular, the enhanced atherosclerosis in diabetes is often discussed in terms of glycation of low-density lipoprotein (LDL), the non-enzymic attachment of glucose to apolipoprotein amino groups. However, glucose can undergo transition-metal-catalysed oxidation under near-physiological conditions in vitro, producing oxidants that possess a reactivity similar to the hydroxyl radical. These oxidants can fragment protein, hydroxylate benzoic acid and induce lipid peroxidation in human LDL. In this study, glycation of LDL in vitro is accompanied by such oxidative processes. However, the oxidation of LDL varies with glucose concentration in a manner which does not parallel changes in protein glycation. Glycation increases in proportion to glucose concentration, whereas in our studies maximal oxidation occurs at a glucose concentration of approx. 25 mM. The modification of LDL resulting from exposure to glucose alters macrophage ceroid accumulation, a process which occurs in the human atherosclerotic plaque. The accumulation of ceroid in macrophages is shown to be related to LDL oxidation rather than LDL glycation, per se, as it too occurs at a maximum of approx. 25 mM. Oxidative sequelae of protein glycation appear to be a major factor in LDL-macrophage interactions, at least with respect to ceroid accumulation. Our observations are discussed in the context of the observed increase in the severity of atherosclerosis in diabetes.

scholarly journals Antioxidative Effects and Inhibition of Human Low Density Lipoprotein OxidationIn Vitroof Polyphenolic Compounds inFlammulina velutipes(Golden Needle Mushroom)

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mohammad Azizur Rahman ◽  
Noorlidah Abdullah ◽  
Norhaniza Aminudin
Keyword(s):  
Low Density Lipoprotein ◽  
Radical Scavenging ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Polyphenolic Compounds ◽  
Oxidative Modification ◽  
Ldl Oxidation ◽  
Total Phenolic ◽  
Low Density ◽  
Antioxidative Effects

Dietary polyphenolic compounds mediate polynomial actions in guarding against multiple diseases. Atherosclerosis is an oxidative stress driven pathophysiological complication where free radical induced oxidative modification of low density lipoprotein (LDL) plays the ground breaking role. Mushrooms have been highly regarded for possessing an antioxidant arsenal. Polyphenolic compounds present in dietary mushrooms seem pertinent in withstanding LDL oxidation en route to controlling atherosclerosis. In this study, the antioxidative effect of five solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ) ofFlammulina velutipeswas evaluated. M : DCM fraction showed the most potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging effect with IC50of 0.86 mg/mL and total phenolic content of 56.36 gallic acid equivalent/g fraction. In LDL oxidation inhibitory tests, M : DCM fraction at 1 µg/mL concentration mostly lengthened the lag time (125 mins) of conjugated diene formation and inhibited the formation of thiobarbituric acid reactive substances (48.71%, at 1 mg/mL concentration). LC-MS/MS analyses of M : DCM fraction identified the presence of polyphenolic substances protocatechuic acid,p-coumaric, and ellagic acid. These chain-breaking polyphenolics might impart the antioxidative effects ofF. velutipes. Thus, mushroom-based dietary polyphenolic compounds might be implicated in slowing down the progression of atherosclerosis.

Intracellular GSH of Streptococcus thermophilus shows anti-oxidative activity against low-density lipoprotein oxidation in vitro and in a hyperlipidaemic hamster model

2018 ◽  
Vol 9 (1) ◽  
pp. 143-152 ◽  
Author(s):  
S. Kusuhara ◽  
M. Ito ◽  
T. Sato ◽  
W. Yokoi ◽  
Y. Yamamoto ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Streptococcus Thermophilus ◽  
Oxidative Modification ◽  
Mass Spectrometry Analysis ◽  
Oxidative Activity ◽  
Ldl Oxidation ◽  
Low Density ◽  
Dependent Manner ◽  
Hamster Model

Streptococcus thermophilus YIT 2001 (ST-1), a lactic acid bacterial strain, was shown to have inhibitory effects on the oxidation of low-density lipoprotein (LDL) and the development of aortic fatty lesions in an animal model, and lower the serum levels of malondialdehyde-modified LDL, an oxidative modification product of LDL, in a clinical trial. This study aimed to identify the intracellular active component of ST-1 associated with anti-oxidative activity against LDL oxidation. High-performance liquid chromatography-electrospray ionisation mass spectrometry analysis after fractionation of the cellular extract by reversed-phase chromatography demonstrated that the active fraction contained reduced glutathione (GSH). GSH showed anti-oxidative activity in a dose-dependent manner, while this activity disappeared following thiol derivatisation. ST-1 had the strongest anti-oxidative activity against LDL oxidation and the highest level of intracellular GSH among five strains of S. thermophilus. In addition, the anti-oxidative activity of ST-1 after thiol derivatisation decreased by about half, which was similar to that of three other strains containing poor or no intracellular GSH or thiol components. Moreover, anti-oxidative activity against LDL oxidation was observed in hyperlipidaemic hamsters fed with high GSH ST-1 cells but not in those given low GSH cells. These findings suggest that intracellular GSH in ST-1 may provide beneficial effects via anti-oxidative activity against LDL oxidation and excess oxidative stress in the blood.

Antioxidants and atherosclerosis

2004 ◽  
Vol 32 (1) ◽  
pp. 156-159 ◽  
Author(s):  
E. Niki
Keyword(s):  
Free Radical ◽  
Vitamin E ◽  
Low Density Lipoprotein ◽  
Radical Scavenging ◽  
Density Lipoprotein ◽  
Active Species ◽  
Oxidative Modification ◽  
Ldl Oxidation ◽  
Low Density ◽  
Mediated Oxidation

The oxidative modification of low-density lipoprotein (LDL) can be induced by various active species by different mechanisms. Vitamin E and other radical-scavenging antioxidants can inhibit the free radical-mediated oxidation of LDL, but they are not effective against LDL oxidation induced by non-radical mechanisms.

scholarly journals Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Cédric Delporte ◽  
Pierre Van Antwerpen ◽  
Luc Vanhamme ◽  
Thierry Roumeguère ◽  
Karim Zouaoui Boudjeltia
Keyword(s):  
Endothelial Cells ◽  
Foam Cell ◽  
Thrombus Formation ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Low Density ◽  
Oxidized Lipoproteins

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFαand IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

scholarly journals A Simple Method for Assessing Copper-Mediated Oxidation of Very-Low-Density Lipoprotein Isolated by Rapid Ultracentrifugation

1998 ◽  
Vol 35 (4) ◽  
pp. 504-514 ◽  
Author(s):  
Jane McEneny ◽  
Elisabeth R Trimble ◽  
Ian S Young
Keyword(s):  
Rapid Method ◽  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Size Exclusion ◽  
Foam Cell Formation ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Simple Method

The association of very-low-density lipoprotein (VLDL) with atherosclerosis remains controversial. However, studies have shown that oxidative modification of VLDL can promote foam cell formation, leading to the development of atherosclerosis. A rapid method is described which will allow the significance of VLDL oxidation to be assessed in clinical studies. VLDL was isolated from heparinized plasma by a 1-h, single spin ultracentrifugation. Total protein was standardized to 25 mg/L. Oxidation was promoted by the addition of copper ions (17.5 μmol/L, final concentration) incubated at 37°C. Conjugated diene production was followed at 234 nm. Total assay preparation time was 2 h. Urate greatly inhibited the oxidation of VLDL and was successfully removed by size exclusion chromatography. VLDL isolated from frozen plasma (−70°C) was stable for 15 weeks. This simple, rapid method for the isolation of VLDL may be applied to assess the significance of VLDL oxidation in disease.

scholarly journals 5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein

1991 ◽  
Vol 278 (1) ◽  
pp. 163-169 ◽  
Author(s):  
W Jessup ◽  
V Darley-Usmar ◽  
V O'Leary ◽  
S Bedwell
Keyword(s):  
Low Density Lipoprotein ◽  
Radical Scavenging ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Ldl Oxidation ◽  
Low Density ◽  
Lipoxygenase Pathway ◽  
Lipoxygenase Inhibitors ◽  
Radical Scavenging Properties ◽  
Mediated Oxidation

The concentration-dependent effects of a series of lipoxygenase inhibitors and antioxidants on the macrophage-mediated oxidative modification of low-density lipoprotein (LDL) were measured. Their influence on macrophage 5-lipoxygenase pathway activity was also studied over the same concentration range. No correlation between inhibition of 5-lipoxygenase and of macrophage-mediated oxidation of LDL was observed. The capacity of the compounds to prevent cell-mediated modification of LDL could be explained in terms of their activity as either aqueous- or lipid-peroxyl radical scavengers. Two potent 5-lipoxygenase inhibitors (MK 886 and Revlon 5901), which had no radical-scavenging properties, were unable to block LDL modification. It is concluded that 5-lipoxygenase is not essential for LDL oxidation by macrophages.

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