Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals

Hermann, Marcela; Kapiotis, Stylianos; Hofbauer, Roland; Exner, Markus; Seelos, Christian; Held, Irmtraud; Gmeiner, Bernhard

doi:10.1016/s0014-5793(99)00043-5

Cited by 44 publications

(34 citation statements)

References 39 publications

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“…23,24 However, local concentrations within specific tissue sites or accumulation of salicylate or active metabolites within a target cell type could reach the levels used in our model system. Other studies have suggested that salicylate potentially influences the intracellular redox state, 25 and we have published several studies showing that Ang II signaling in the cardiac fibroblast is influenced by antioxidants such as N-acetylcysteine. 10,11 Thus, whether salicylate inhibits the phosphorylation of PYK2 and c-Src by altering the intracellular redox state requires further investigation.…”

Section: Wang and Brechermentioning

confidence: 81%

Salicylate Inhibits Phosphorylation of the Nonreceptor Tyrosine Kinases, Proline-Rich Tyrosine Kinase 2 and c-Src

Wang

Brecher

2001

Hypertension

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Abstract-The anti-inflammatory effects of salicylate are well known, but the intracellular mechanisms underlying those effects remain to be clarified and are not explained solely by an influence on cyclooxygenase activity. In the present study, we have used cardiac fibroblasts stimulated by either angiotensin II (Ang II) or platelet-derived growth factor (PDGF) to demonstrate an inhibitory effect of salicylate on the phosphorylation of the nonreceptor tyrosine kinases, proline-rich tyrosine kinase 2 (PYK2) and c-Src, by immunoprecipitation and immunoblotting methods. This inhibition was dose dependent, with a clear effect observed at concentrations between 5 and 20 mmol/L salicylate. Intracellular Ca 2ϩ chelation and protein kinase C (PKC) inhibition reduced Ang II and PDGF-induced PYK2 and c-Src phosphorylation. Salicylate significantly inhibited the phosphorylation of both of the tyrosine kinases activated by either ionophore A23187 or thapsigargin treatment, which led to an elevation of cytosolic Ca 2ϩ . Activation of PKC by phorbol ester phosphorylated both PYK2 and Src, and this effect also was attenuated by salicylate. In contrast, salicylate had no effect on either the transactivation of the epidermal growth factor receptor by Ang II or the phosphorylation of phospholipase C-␥ by PDGF. These studies indicate a novel site of action for salicylate on PYK2 and c-Src phosphorylation and suggest that this inhibitory effect on these important signaling intermediates may be through a Ca 2ϩ -and PKC-dependent mechanism. (Hypertension. 2001;37:148-153.)

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Section: Wang and Brechermentioning

confidence: 81%

Salicylate Inhibits Phosphorylation of the Nonreceptor Tyrosine Kinases, Proline-Rich Tyrosine Kinase 2 and c-Src

Wang

Brecher

2001

Hypertension

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“…Phosphate buffer was prepared to contain 50 mM sodium phosphate, 10 mM NaCl, 0.1 mM diethylenetriaminepentaacetic acid, pH 7.4 (21). To eliminate the contamination of transition metals such as copper and iron, the phosphate buffer was treated by Chelex 100 according to the instruction manual from Bio-Rad.…”

Section: Methodsmentioning

confidence: 99%

“…A cell-free system was used to avoid the influence of other cellular enzymes and antioxidants and the interaction of ONOO Ϫ with other ROS and RNS in the cell. DNA damage and oxidation of LDL were determined as indexes of ONOO Ϫ -induced oxidative damage, because DNA is a sensitive target (18,19), and lipoproteins are also sensitive to ONOO Ϫ -induced oxidative damage (20,21).…”

mentioning

confidence: 99%

Metallothionein Inhibits Peroxynitrite-induced DNA and Lipoprotein Damage

Cai¹,

Klein²,

Kang³

2000

Journal of Biological Chemistry

152

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Previous studies have demonstrated that metallothionein functions as an antioxidant that protects against oxidative DNA, protein, and lipid damage induced by superoxide anion, hydrogen peroxide, hydroxyl radical, and nitric oxide. The present study was undertaken to test the hypothesis that metallothionein also protects from DNA and lipoprotein damage induced by peroxynitrite, an important reactive nitrogen species that causes a diversity of pathological processes. A cell-free system was used. DNA damage was detected by the mobility of plasmid DNA in electrophoresis. Oxidation of low density lipoprotein was measured by a thiobarbituric acidreactive substance, which was confirmed by lipid hydroperoxide assay. Plasmid DNA damage and low density lipoprotein oxidation were induced by 3-morpholinosydnomine, which produces peroxynitrite through the reaction between nitric oxide and superoxide anion or by synthesized peroxynitrite directly. DNA damage by 3-morpholinosydnomine was prevented by both metallothionein and superoxide dismutase, whereas the damage caused by peroxynitrite was prevented by metallothionein only. The oxidation of low density lipoprotein by 3-morpholinosydnomine and peroxynitrite was also significantly inhibited by metallothionein. This study thus demonstrates that metallothionein may react directly with peroxynitrite to prevent DNA and lipoprotein damage induced by this pathological reactive nitrogen species.

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“…Apart from this, subjects were asked to maintain their usual diet. During the study subjects were not allowed to take vitamin supplements or aspirin, which is a radical scavenger (Kuhn et al, 1995;Hermann et al, 1999). Therefore they were provided with acetaminophen (paracetamol).…”

Section: Design and Treatmentmentioning

confidence: 99%

Effect of phenol-rich extra virgin olive oil on markers of oxidation in healthy volunteers

et al. 2001

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Objective: We studied whether consumption of phenol-rich extra virgin olive oil affects the susceptibility of low density lipoproteins (LDL) to oxidation and other markers of oxidation in humans. Design: Randomized cross-over intervention trial, strati®ed according to sex, age and energy intake. Setting: Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands. Subjects: Forty-six healthy men and women completed the study. Intervention: Subjects consumed two diets supplying 69 g per day of extra virgin olive oil either rich or poor in phenols for 3 weeks each. The mean difference in phenol intake between the treatments was 18 mg per day. Vitamin E intake was low during the whole study. Fasting blood samples were taken twice at the end of each period. Results: Resistance of LDL and high density lipoprotein (HDL) to oxidation was not affected by treatment. The mean lag time of copper-induced formation of conjugated dienes was 1.6 min shorter in LDL and 0.4 min longer in HDL after the high phenol diet. Other markers of antioxidant capacity in plasma were also not affected: mean lipid hydroperoxides were 0.07 mmolal higher, mean malondialdehydes were 0.001 mmolal higher, mean protein carbonyls were 0.001 nmolamg protein lower, and the mean ferric reducing ability of plasma (FRAP) was 0.006 mmolal higher after the high phenol diet. All 95% con®dence intervals enclosed zero. Serum cholesterol concentrations were not affected by the treatment.

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Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals

Cited by 44 publications

References 39 publications

Salicylate Inhibits Phosphorylation of the Nonreceptor Tyrosine Kinases, Proline-Rich Tyrosine Kinase 2 and c-Src

Salicylate Inhibits Phosphorylation of the Nonreceptor Tyrosine Kinases, Proline-Rich Tyrosine Kinase 2 and c-Src

Metallothionein Inhibits Peroxynitrite-induced DNA and Lipoprotein Damage

Effect of phenol-rich extra virgin olive oil on markers of oxidation in healthy volunteers

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