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

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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Antioxidants and atherosclerosis

Biochemical Society Transactions ◽

10.1042/bst0320156 ◽

2004 ◽

Vol 32 (1) ◽

pp. 156-159 ◽

Cited By ~ 39

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.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/403023 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 14

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.

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Oxidative modification of triacylglycerol-rich lipoproteins

Biochemical Society Transactions ◽

10.1042/bst0311062 ◽

2003 ◽

Vol 31 (5) ◽

pp. 1062-1065 ◽

Cited By ~ 15

Author(s):

I.S. Young ◽

C. McFarlane ◽

J. McEneny

Keyword(s):

Particle Size ◽

Fatty Acid Composition ◽

Arterial Wall ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Oxidative Modification ◽

Low Density ◽

Lipoprotein Oxidation ◽

Oxidative Reactions ◽

Mediated Oxidation

Lipoprotein oxidation is thought to play a pivotal role in the evolution of atherosclerosis. Low-density lipoprotein (LDL) is the main source of oxidized lipid in the arterial wall. Oxidation of LDL alters its properties in a number of ways, making it more atherogenic, but oxidation of other lipoprotein classes may also be important. Common mechanisms are likely to contribute to the oxidation of all lipoprotein classes, with enzyme-mediated oxidation likely to be most important. Antioxidant content, fatty acid composition, particle size and the presence of seeding hydroperoxides also influence oxidative reactions. Larger triglyceride-rich lipoproteins are less likely to enter the arterial wall than LDL, but when oxidized will deliver a greater oxidant load to the arterial wall.

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

Biochemical Journal ◽

10.1042/bj3140577 ◽

1996 ◽

Vol 314 (2) ◽

pp. 577-585 ◽

Cited By ~ 29

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.

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

Beneficial Microbes ◽

10.3920/bm2017.0065 ◽

2018 ◽

Vol 9 (1) ◽

pp. 143-152 ◽

Cited By ~ 1

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.

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