Copper and Copper-Nicotinic Acid Complexes Mediated Oxidation of High Density Lipoprotein

ElSaadani, Mohamed; Esterbauer, Hermann; Jürgens, Günther; El‐Sayed, Mohamed M.; Nassar, Ahmed; Goher, M. A. S.; Holasek, A.

doi:10.1007/978-1-4684-5568-7_59

Cited by 45 publications

(52 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LDL Oxidation Assays-LDL lipid peroxides were measured using the method of El-Saadani et al (48). LDL (50 -150 g of protein), in a volume of no more than 100 l, was added to 1 ml of color reagent (0.2 M KH 2 PO 4 , 0.12 M KI, 0.15 mM NaN 3 , 2 g of Triton X-100/liter, 0.1 g of benzalkonium chloride/liter, 10 M ammonium molybdate, 20 M BHT, 25 M EDTA, pH 6.2) and incubated in the dark for 30 min at room temperature; light absorbance at 365 nm was then measured and lipid peroxides were quantified by comparison with a H 2 O 2 standard curve.…”

Section: Methodsmentioning

confidence: 99%

Secretory Sphingomyelinase, a Product of the Acid Sphingomyelinase Gene, Can Hydrolyze Atherogenic Lipoproteins at Neutral pH

Schissel¹,

Jiang²,

Tweedie-Hardman³

et al. 1998

Journal of Biological Chemistry

303

263

View full text Add to dashboard Cite

The subendothelial aggregation and retention of low density lipoprotein (LDL) are key events in atherogenesis, but the mechanisms in vivo are not known. Previous studies have shown that treatment of LDL with bacterial sphingomyelinase (SMase) in vitro leads to the formation of lesion-like LDL aggregates that become retained on extracellular matrix and stimulate macrophage foam cell formation. In addition, aggregated human lesional LDL, but not unaggregated lesional LDL or plasma LDL, shows evidence of hydrolysis by an arterial wall SMase in vivo, and several arterial wall cell types secrete a SMase (S-SMase). S-SMase, however, has a sharp acid pH optimum using a standard in vitro SMmicelle assay. Thus, a critical issue regarding the potential role of S-SMase in atherogenesis is whether the enzyme can hydrolyze lipoprotein-SM, particularly at neutral pH. We now show that S-SMase can hydrolyze and aggregate native plasma LDL at pH 5.5 but not at pH 7.4. Remarkably, LDL modified by oxidation, treatment with phospholipase A 2 , or enrichment with apolipoprotein CIII, which are modifications associated with increased atherogenesis, is hydrolyzed readily by S-SMase at pH 7.4. In addition, lipoproteins from the plasma of apolipoprotein E knock-out mice, which develop extensive atherosclerosis, are highly susceptible to hydrolysis and aggregation by S-SMase at pH 7.4; a high SM:PC ratio in these lipoproteins appears to be an important factor in their susceptibility to S-SMase. Most importantly, LDL extracted from human atherosclerotic lesions, which is enriched in sphingomyelin compared with plasma LDL, is hydrolyzed by S-SMase at pH 7.4 10-fold more than same donor plasma LDL, suggesting that LDL is modified in the arterial wall to increase its susceptibility to S-SMase. In summary, atherogenic lipoproteins are excellent substrates for S-SMase, even at neutral pH, making this enzyme a leading candidate for the arterial wall SMase that hydrolyzes LDL-SM and causes subendothelial LDL aggregation.

show abstract

Section: Methodsmentioning

confidence: 99%

Secretory Sphingomyelinase, a Product of the Acid Sphingomyelinase Gene, Can Hydrolyze Atherogenic Lipoproteins at Neutral pH

Schissel¹,

Jiang²,

Tweedie-Hardman³

et al. 1998

Journal of Biological Chemistry

303

263

View full text Add to dashboard Cite

show abstract

“…The extent of LDL modification was assessed by electrophoretic mobility in 1% agarose. Lipid peroxide levels in oxidized LDL were measured by quantifying the oxidation of iodide to iodine (I 3 ), as described (28). Thiobarbituric acid-reactive substances in preparations of cell-modified LDL were measured as described (29).…”

Section: Methodsmentioning

confidence: 99%

Class A Scavenger Receptor Up-regulation in Smooth Muscle Cells by Oxidized Low Density Lipoprotein

Mietus‐Snyder¹,

Gowri²,

Pitas³

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…The tri-iodide method of El-Saadani et al [60], modified slightly as described previously [56], was used to determine lipid hydroperoxides in oxidised LDL (100 µg protein/ml). This concentration of oxidised LDL was used, rather than 50 µg protein/ml, because the lipid hydroperoxide assay is less sensitive than the conjugated diene assay.…”

Section: Lipid Hydroperoxide Assaymentioning

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

View full text Add to dashboard Cite

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.

show abstract

Copper and Copper-Nicotinic Acid Complexes Mediated Oxidation of High Density Lipoprotein

Cited by 45 publications

References 8 publications

Secretory Sphingomyelinase, a Product of the Acid Sphingomyelinase Gene, Can Hydrolyze Atherogenic Lipoproteins at Neutral pH

Secretory Sphingomyelinase, a Product of the Acid Sphingomyelinase Gene, Can Hydrolyze Atherogenic Lipoproteins at Neutral pH

Class A Scavenger Receptor Up-regulation in Smooth Muscle Cells by Oxidized Low Density Lipoprotein

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

Contact Info

Product

Resources

About