The oxidation of low density lipoprotein by cells or iron is inhibited by zinc

Wilkins, Gary M.; Leake, David S.

doi:10.1016/0014-5793(94)80468-0

Cited by 46 publications

(26 citation statements)

References 25 publications

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“…Zn2+ is a known inhibitor of endogenous plasma GSH-Px (21) that, unlike transition metal ions, does not promote free radical generation (22,23). In addition, ZnCl2 inhibits the plasma but not the erythrocyte form of GSH-Px, excluding the possibility that the results obtained were due to erythrocyte contamination.…”

Section: Measurement Ofmentioning

confidence: 99%

Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.

Freedman

Frei²,

Welch³

et al. 1995

J. Clin. Invest.

136

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GSH peroxidase (Px) catalyzes the reduction of lipid hydroperoxides (LOOH), known metabolic products of platelets and vascular cells. Because interactions between these cells are modulated by nitric oxide (NO) and LOOH inactivate NO, we investigated the effect of GSH-Px on the inhibition of platelet function by the naturally occurring S-nitrosothiol, S-nitroso-glutathione (SNO-Glu). Concentrations of SNO-Glu that alone did not inhibit platelet function (subthreshold inhibitory concentrations) were added to plateletrich plasma together with GSH-Px (0.2-20 U/ml); this led to a dose-dependent inhibition of platelet aggregation with an IC50 of 0.6 U/ml GSH-Px. In the presence of subthreshold inhibitory concentrations of SNO-Glu, the LOOH, 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid, increased platelet aggregation, an effect reversed by GSH-Px. Glutathione and SNO-Glu were equally effective as cosubstrates for GSHPx. Incubation of SNO-Glu with GSH-Px for 1 min led to a 48.5% decrease in the concentration of SNO-Glu. Incubation of SNO-Glu with serum albumin led to the formation of S-nitroso-albumin, an effect enhanced by GSH-Px. These observations suggest that GSH-Px has two functions: reduction of LOOH, thereby preventing inactivation of NO, and metabolism of SNO-Glu, thereby liberating NO and/or supporting further transnitrosation reactions. (J. Clin. Invest. 1995. 96:394-400.) Key words: nitric oxide * S-nitrosothiols * endothelium-derived relaxing factor * lipid peroxides glutathione peroxidase

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Section: Measurement Ofmentioning

confidence: 99%

Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.

Freedman

Frei²,

Welch³

et al. 1995

J. Clin. Invest.

136

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“…3,4 These data are consistent with some, but not all, epidemiological studies on the potential links between iron and cardiovascular disease. [5][6][7][8] Zinc ions have been reported to modulate oxidant damage via the displacement of iron and copper from oxidationsensitive sites on erythrocyte membranes, 9 LDL, 10 or liposomes. 11 Epidemiological data indicate that elevated serum zinc levels may be protective against disease.…”

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confidence: 99%

Accumulation of Zinc in Human Atherosclerotic Lesions Correlates With Calcium Levels But Does Not Protect Against Protein Oxidation

Stadler

Stanley

Heeneman

et al. 2008

ATVB

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Objective-Oxidized lipids and proteins, as well as decreased antioxidant levels, have been detected in human atherosclerotic lesions, with oxidation catalyzed by iron and copper postulated to contribute to lesion development. Zinc has been postulated to displace iron from critical sites and thereby protect against damage. In this study, metal ion and protein oxidation levels were quantified in human carotid and abdominal artery specimens containing early-to-advanced lesions, to determine whether zinc concentrations correlate inversely with iron levels and protein oxidation. Methods and Results-Metal ions were quantified by EPR and inductively coupled plasma mass spectroscopy. Native and oxidized protein side-chains were quantified by high-performance liquid chromatography. A therosclerosis is a multifactorial disease to which many factors contribute; defining the role of each of these has proved to be problematic. Oxidation, and in particular that of low-density lipoproteins (LDL), has been linked to disease development, 1 although the significance of this process has not been fully established (reviewed 2 ). Previous studies have variously implicated lipoxygenase, peroxynitrite, myeloperoxidase, oxygen radicals, and metal-ions in lesion oxidation (reviewed 2 ). In the case of metal ions, a correlation between iron accumulation and the extent of protein (but not lipid) oxidation has been reported for human lesions. 3 Cholesterol ester and cholesterol accumulation also correlate positively with iron, suggesting that these processes are interlinked. 3,4 These data are consistent with some, but not all, epidemiological studies on the potential links between iron and cardiovascular disease. [5][6][7][8] Zinc ions have been reported to modulate oxidant damage via the displacement of iron and copper from oxidationsensitive sites on erythrocyte membranes, 9 LDL, 10 or liposomes. 11 Epidemiological data indicate that elevated serum zinc levels may be protective against disease. 12 Serum or plasma measurements of zinc in people with established atherosclerosis indicate that low zinc levels are associated with increased disease 13,14 and a postmortem study has reported lower tissue levels of zinc in the abdominal aorta of patients who died of heart disease compared to other causes. 15 In contrast, zinc supplementation of the human diet does not affect the susceptibility of LDL to oxidation ex vivo 16,17 or the concentrations of LDL-cholesterol, total cholesterol, or triglycerides, but has an adverse effect on high-density lipoprotein levels, suggesting that high serum zinc levels may promote disease. 17 Elevated zinc may stimulate the formation of oxidants and inhibit protective enzymes in some cells. 18 Atherosclerotic lesions of cholesterol-fed rabbits contain elevated levels of iron and reduced levels of zinc. 19 -21 Zinc supplementation, via dietary feeding, reduced lesion area despite insignificant changes in lesion zinc concentrations; these changes were ascribed to a displacement of iron by zinc. 20 Zinc supplement...

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“…27 Zn may play an antiatherogenic role through the inhibition of inflammation and oxidative stress, consequently inhibiting the oxidation of LDL particles by macrophages and endothelial cells. 20,[28][29][30] LDL(-) (a lipid peroxidation marker) induces atherogenesis by a variety of biological activities including cytotoxicity and leukocyte recruitment that actively contribute to the alteration of the vascular endothelium, increasing CV risk. [8][9][10] Many reports have described the increased LDL(-) levels in patients with CV disease risk, including CKD.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, cellular enrichment with Zn has been shown to attenuate or prevent TNF-induced endothelial cell injury. 32 According to Meerarani et al, 29 Zn deficiency increases apoptotic cell death induced by TNF-α, and these authors have showed that Zn supplementation attenuates apoptosis. Moreover, several potential mechanisms may account for the benefits of Zn, the increased activity and the expression of stress-related proteins and antioxidant proteins, including metallothioneins (MT), chaperones, ApoJ, Poly (ADP-Ribose) polymerase-1 (PARP-1) methionine sulfoxide reductase (Msr), and superoxide dismutase (SOD).…”

Section: -13mentioning

confidence: 99%

Reduced Plasma Zinc Levels, Lipid Peroxidation, and Inflammation Biomarkers Levels in Hemodialysis Patients: Implications to Cardiovascular Mortality

Lobo¹,

Stockler‐Pinto²,

Farage³

et al. 2013

Renal Failure

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Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(-)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 AE 12.7 years, 62.2 AE 51.4 months on dialysis and BMI 24.3 AE 4.1 kg/ m 2 ) were studied and compared to 20 healthy individuals (9 men, 51.6 AE 15.6 years, BMI 25.2 AE 3.9 kg/m 2 ) and followed for 24 months to investigate the risks for CV mortality. LDL(-) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 AE 16.1 μg/dL) and high-LDL(-) (0.18 AE 0.12 U/L) and TNF-α (5.5 AE 2.2 pg/mL) levels when compared to healthy subjects (78.8 AE 9.4μ g/dL, 0.10 AE 0.08U/L, 2.4 AE 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r ¼ -0.49; p ¼ 0.0001) and LDL(-) (r ¼ -0.33; p ¼ 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.

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The oxidation of low density lipoprotein by cells or iron is inhibited by zinc

Cited by 46 publications

References 25 publications

Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.

Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.

Accumulation of Zinc in Human Atherosclerotic Lesions Correlates With Calcium Levels But Does Not Protect Against Protein Oxidation

Reduced Plasma Zinc Levels, Lipid Peroxidation, and Inflammation Biomarkers Levels in Hemodialysis Patients: Implications to Cardiovascular Mortality

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