Ascorbate prevents prooxidant effects of urate in oxidation of human low density lipoprotein

Abuja, Peter M.

doi:10.1016/s0014-5793(99)00231-8

Cited by 113 publications

(95 citation statements)

References 17 publications

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“…21 Despite this, several studies have demonstrated that uric acid can be prooxidative and may generate free radicals. [22][23][24][25] The ability to activate p38 MAPK, NF-kB, and AP-1, as well as to increase MCP-1 expression, is consistent with an oxidantdriven pathway. 26,27 In conclusion, we have found that uric acid can induce inflammatory pathways in rat VSMCs in vitro, with activation of p38 MAPK, NF-B, and AP-1 and increased expression of COX-2 and MCP-1.…”

Section: Discussionmentioning

confidence: 56%

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2

et al. 2003

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Abstract-Previous studies have reported that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation in vitro. We hypothesized that uric acid may also have direct proinflammatory effects on VSMCs. Crystal-and endotoxin-free uric acid was found to increase VSMC monocyte chemoattractant protein-1 (MCP-1) expression in a time-and dose-dependent manner, peaking at 24 hours. Increased mRNA and protein expression occurred as early as 3 hours after uric acid incubation and was partially dependent on posttranscriptional modification of MCP-1 mRNA. In addition, uric acid activated the transcription factors nuclear factor-B and activator protein-1, as well as the MAPK signaling molecules ERK p44/42 and p38, and increased cyclooxygenase-2 (COX-2) mRNA expression. Inhibition of p38 (with SB 203580), ERK 44/42 (with UO126 or PD 98059), or COX-2 (with NS398) each significantly suppressed uric acid-induced MCP-1 expression at 24 hours, implicating these pathways in the response to uric acid. The ability of both N-acetyl-cysteine and diphenyleneionium (antioxidants) to inhibit uric acid-induced MCP-1 production suggested involvement of intracellular redox pathways. Uric acid regulates critical proinflammatory pathways in VSMCs, suggesting it may have a role in the vascular changes associated with hypertension and vascular disease.

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Section: Discussionmentioning

confidence: 56%

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2

et al. 2003

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“…This can be explained on several accounts. It has been suggested that 60% of FRAP activity is contributed by uric acid and hyperuricemia as part of the metabolic syndrome [2,[42][43][44] may be responsible for higher FRAP in the NAFLD group. The increase in FRAP levels may occur as a compensatory phenomenon in NA-FLD patients to protect against OS.…”

Section: Discussionmentioning

confidence: 99%

Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease

et al. 2008

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Purpose Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases. Methods A total of 44 patients with ALD and 32 patients with NAFLD and 25 apparently healthy controls were included in the study. Redox status was estimated by measuring oxidative stress (superoxide dismutase (SOD) and lipid peroxidation products as thiobarbituric acid reactive substances (TBARS)) and antioxidant status (ferric reducing ability of plasma (FRAP) and vitamin C). Results TBARS level was raised significantly in both ALD (3.5 (2.3-9.4) vs. 1.8 (0.5-4.1) nmol/ml; P = 0.0001) and NAFLD (5.1 (1-10.2) vs. 1.82 (0.51-4.1) nmol/ml; P = 0.0001) as compared with controls, but was not different between ALD and NAFLD. SOD was significantly higher in ALD as compared to NAFLD (2.4 (1.3-7.8) vs. 0.68 (0.05-19.1) U/ml; P = 0.0001) and controls (1.12 (0.01-3.5) U/ml; P = 0.001). FRAP was lower in ALD as compared with 3) lmol of Fe +2 liberated; P = 0.001) but similar to that of controls (340.9 (141.5-697.5) lmol of Fe +2 liberated). Conclusions ALD patients have a higher degree of redox imbalance as compared with NAFLD patients

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“…Subsequent studies have revealed similar properties in other common antioxidants, including flavonoids [30], nonflavonoid phenols [36], cysteine [37,38], and urate [39][40][41]. The effects of ascorbate are further complicated by the fact that dehydroascorbate, the product of its two-electron oxidation, can itself act as both a pro-oxidant and an antioxidant toward LDL [24,26,35,42].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

Horsley

Burkitt

Jones

et al. 2007

Archives of Biochemistry and Biophysics

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Subject area: Systems biochemistryAbbreviations: BCDS, bathocuproine disulphonic acid; DMPO,5, EPR, electron paramagnetic resonance; 13-HPODE, 13(S)-hydroperoxyoctadeca-9Z,11E-dienoic acid 2 ABSTRACTOxidised low density lipoprotein (LDL) may be involved in the pathogenesis of atherosclerosis.We have therefore investigated the mechanisms underlying the antioxidant/pro-oxidant behavior of dehydroascorbate, the oxidation product of ascorbic acid, toward LDL incubated with Cu 2+ ions. By monitoring lipid peroxidation through the formation of conjugated dienes and lipid hydroperoxides, we show that the pro-oxidant activity of dehydroascorbate is critically dependent on the presence of lipid hydroperoxides, which accumulate during the early stages of oxidation.Using electron paramagnetic resonance spectroscopy, we show that dehydroascorbate amplifies the generation of alkoxyl radicals during the interaction of copper ions with the model alkyl hydroperoxide, tert-butylhydroperoxide. Under continuous-flow conditions, a prominent doublet signal was detected, which we attribute to both the erythroascorbate and ascorbate free radicals.On this basis, we propose that the pro-oxidant activity of dehydroascorbate toward LDL is due to its known spontaneous interconversion to erythroascorbate and ascorbate, which reduce Cu 2+ to Cu + and thereby promote the decomposition of lipid hydroperoxides. Various mechanisms, including copper chelation and Cu + oxidation, are suggested to underlie the antioxidant behavior of dehydroascorbate in LDL that is essentially free of lipid hydroperoxides.

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Ascorbate prevents prooxidant effects of urate in oxidation of human low density lipoprotein

Cited by 113 publications

References 17 publications

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2

Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

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