Cu(I) Availability Paradoxically Antagonizes Antioxidant Consumption and Lipid Peroxidation during the Initiation Phase of Copper-Induced LDL Oxidation

Bagnati, Marco; Bordone, Renato; Perugini, C.; Cau, C.; Albano, Emanuele; Bellomo, Giorgio

doi:10.1006/bbrc.1998.9777

Cited by 24 publications

(15 citation statements)

References 23 publications

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“…Uric acid is, indeed, a powerful reductant of Cu(II) in aqueous solutions and its availability could explain both the antioxidant and prooxidant effects exerted by uric acid. With regard to the antioxidant activity, we have recently observed that the inclusion of equimolar concentrations of Cu(I), when added together with Cu(II) to an incubation mixture containing isolated human LDL, efficiently prolonged the duration of the lag phase and decreased the initial rate of endogenous α-tocopherol consumption [33]. Moreover, Cu(I) reacts with preformed lipid peroxides with the concomitant formation of lipid alkoxy radicals…”

Section: Discussionmentioning

confidence: 99%

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Bagnati

Perugini

Cau

et al. 1999

Biochemical Journal

130

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The inclusion of uric acid in the incubation medium during copper-induced low-density lipoprotein (LDL) oxidation exerted either an antioxidant or pro-oxidant effect. The pro-oxidant effect, as mirrored by an enhanced formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances and increase in negative charge, occurred when uric acid was added late during the inhibitory or lag phase and during the subsequent extensive propagation phase of copper-stimulated LDL oxidation. The pro-oxidant effect of uric acid was specific for copper-induced LDL oxidation and required the presence of copper as either Cu(I) or Cu(II). In addition, it became much more evident when the copper to LDL molar ratio was below a threshold value of approx. 50. In native LDL, the shift between the antioxidant and the pro-oxidant activities was related to the availability of lipid hydroperoxides formed during the early phases of copper-promoted LDL oxidation. The artificial enrichment of isolated LDL with α-tocopherol delayed the onset of the pro-oxidant activity of uric acid and also decreased the rate of stimulated lipid peroxidation. However, previous depletion of α-tocopherol was not a prerequisite for unmasking the pro-oxidant activity of uric acid, since this became apparent even when α-tocopherol was still present in significant amounts (more than 50% of the original values) in LDL. These results suggest, irrespective of the levels of endogenous α-tocopherol, that uric acid may enhance LDL oxidation by reducing Cu(II) to Cu(I), thus making more Cu(I) available for subsequent radical decomposition of lipid peroxides and propagation reactions.

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Section: Discussionmentioning

confidence: 99%

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Bagnati

Perugini

Cau

et al. 1999

Biochemical Journal

130

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“…As kinetic index of LDL oxidation, lag time was determined graphically [17,18]; maximum rate of oxidation was calculated as the highest value of the first derivative of CD vs time profile. TocOH was measured by HPLC chromatography using a reverse‐phase C18 column and spectrophotometric detection at 292 nm; an external standard was used for calibration [19]. In our preparations, TocOH content of LDL was 5±0.3 mol/mol LDL.…”

Section: Methodsmentioning

confidence: 98%

Mechanistic aspects of the relationship between low‐level chemiluminescence and lipid peroxides in oxidation of low‐density lipoprotein

et al. 1999

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In this study oxidation of low-density lipoprotein (LDL) induced by different Cu 2+ concentrations was investigated. Lipid peroxidation was assessed by monitoring low-level chemiluminescence (LL-CL), conjugated diene hydroperoxide (CD) and K K-tocopherol (TocOH), the major lipophilic antioxidant in LDL. At high Cu 2+ concentration, LDL oxidation was characterised by CD formation, LL-CL emission and TocOH consumption. At low Cu 2+ concentration, CD formation was independent of LL-CL and occurred in the presence of TocOH. Thus, two different mechanisms lead to lipid peroxide formation in LDL. The combination of CD assay and LL-CL monitoring makes it possible to distinguish the autocatalytic mechanism of CD formation and that associated with TocOH, found at a high and a low rate of initiation, respectively. z 1999 Federation of European Biochemical Societies.

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“…Studies have shown this not to be the case. Cu + does not oxidize LDL efficiently, and antagonizes α-tocopherol depletion and lipid peroxidation under certain conditions (30).…”

Section: Discussionmentioning

confidence: 96%

Cu²⁺‐induced low density lipoprotein peroxidation is dependent on the initial O₂ concentration: An O₂ consumption study

Lodge

Traber

Sadler

2000

Lipids

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Atherosclerotic plaques form in the arterial intima, where low density lipoprotein (LDL) is thought to be oxidatively modified at sites which may contain catalytic amounts of copper in the presence of low O2 tension. We have investigated O2 consumption during LDL peroxidation induced by Cu2+ ions in vitro and found two phases: a lag phase followed by a phase of rapid O2 consumption. The length of the lag phase was dependent on Cu2+ and on initial O2 concentrations; increasing either decreased the lag time; however, LDL. concentration had no effect. LDL-induced Cu2+ reduction, however, was not affected by low initial O2 concentrations, suggesting that O2 is not required for LDL-mediated reduction of Cu2+. Following the lag phase, O2 consumption was dependent upon LDL or initial O2 concentrations; Cu2+ concentrations had little effect, suggesting that the propagation phase is more dependent on the presence of LDL lipids and O2 as substrates for the reaction. In summary, LDL peroxidation takes place in the presence of Cu2+ at low O2 tension; however, the reaction is dependent upon initial O2 concentrations; increases shorten the lag phase and accelerate O2 consumption.

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Cu(I) Availability Paradoxically Antagonizes Antioxidant Consumption and Lipid Peroxidation during the Initiation Phase of Copper-Induced LDL Oxidation

Cited by 24 publications

References 23 publications

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Mechanistic aspects of the relationship between low‐level chemiluminescence and lipid peroxides in oxidation of low‐density lipoprotein

Cu²⁺‐induced low density lipoprotein peroxidation is dependent on the initial O₂ concentration: An O₂ consumption study

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Cu(I) Availability Paradoxically Antagonizes Antioxidant Consumption and Lipid Peroxidation during the Initiation Phase of Copper-Induced LDL Oxidation

Cited by 24 publications

References 23 publications

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Mechanistic aspects of the relationship between low‐level chemiluminescence and lipid peroxides in oxidation of low‐density lipoprotein

Cu2+‐induced low density lipoprotein peroxidation is dependent on the initial O2 concentration: An O2 consumption study

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Cu²⁺‐induced low density lipoprotein peroxidation is dependent on the initial O₂ concentration: An O₂ consumption study