Accumulation of altered aspartyl residues in erythrocyte membrane proteins from patients with sporadic amyotrophic lateral sclerosis.

Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal l-isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an oxidative microenvironment. The presence of isopeptide bonds impairs protein structure/function. To minimize the damage, IsoAsp can be "repaired" by the protein l-isoaspartyl/d-aspartyl O-methyltransferase (PIMT) and S-adenosylmethionine (AdoMet) is the methyl donor of this reaction.

Effect of Annurca apple polyphenols on human HaCaT keratinocytes proliferation.

Polyphenols have been demonstrated to have clear antioxidant activities in vitro. However, in complex biological systems, they exhibit additional properties, which are yet poorly understood. The apple is among the most consumed fruits worldwide, and several studies suggest that apple polyphenols could play a role in the prevention of degenerative diseases.

Abnormal isoaspartyl residues in erythrocyte membranes from psoriatic patients.

Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an oxidative microenvironment. The presence of isopeptide bonds impairs protein structure/function and can trigger autoimmune responses. To minimize the damage, IsoAsp can be "repaired" by a specific L-isoaspartate-(D-aspartate)-protein-O-methyltransferase.

C-reactive protein is released in the coronary circulation and causes endothelial dysfunction in patients with acute coronary syndromes.

Background: C-reactive protein (CRP) plasma levels correlate with cardiovascular events. Although a direct role for CRP in atherothrombosis has been suggested, at the moment little is known about its involvement in the pathophysiology of acute coronary syndromes (ACS). Thus, the aim of this study was to determine whether CRP is produced in the culprit lesion and released within the coronary circulation of patients with ACS and whether it may affect coronary endothelial function.

Protective effect of polyphenols from Glycyrrhiza glabra against oxidative stress in Caco-2 cells.

In the present article, we have investigated the antioxidant properties of methanolic liquorice polyphenol extracts (LPE(s)). Polyphenol extraction was performed with 60% and 100% methanol. Analysis of LPE(s) by thin-layer chromatography revealed that a higher amount of polyphenols was recovered by extraction with 60% methanol.

Impaired transmethylation potential in Parkinson's disease patients treated with L-Dopa.

Hyperhomocysteinaemia was reported in patients with Parkinson's disease (PD) treated with l-Dopa. The increase in plasma concentration of this sulfur compound arises from the massive methylation of the drug operated by the enzyme catechol-O-methyltransferase (COMT), which acts as a powerful sink of methyl groups. The contemporary occurrence of C677T polymorphism in homozygosity, leading to a temperature-labile variant of the MTHFR enzyme, induces an even more marked increase in tHcy.

Protein isoaspartate methyltransferase prevents apoptosis induced by oxidative stress in endothelial cells: role of Bcl-Xl deamidation and methylation.

Background: Natural proteins undergo in vivo spontaneous post-biosynthetic deamidation of specific asparagine residues with isoaspartyl formation. Deamidated-isomerized molecules are both structurally and functionally altered. The enzyme isoaspartyl protein carboxyl-O-methyltransferase (PCMT; EC 2.

In vivo effect of the natural antioxidant hydroxytyrosol on cyclosporine nephrotoxicity in rats.

Background: Cyclosporine A (CsA) is the first-line immunosuppressant used in transplant patients and in auto- immune diseases. Nephrotoxicity is the major limitation of CsA use. Although the mechanisms of nephrotoxicity have not been completely defined, some evidence suggests that reactive oxygen species (ROS) play a causal role.

Effect of reddening-ripening on the antioxidant activity of polyphenol extracts from cv. 'Annurca' apple fruits.

Apple is among the most consumed fruits worldwide, and several studies suggest that apple polyphenols could play a role in the prevention of degenerative diseases. 'Annurca' apple fruit undergoes, after harvest, a typical reddening treatment to turn the apples' skin red, and it is noted for its high firmness. This paper reports the effect of reddening-ripening treatment on polyphenol concentration and antioxidant activity of both peel and flesh extracts.

Accumulation of altered aspartyl residues in erythrocyte proteins from patients with Down's syndrome.

Spontaneous protein deamidation of labile Asn residues, generating L-isoaspartates and D-aspartates, is associated with cell aging and is enhanced by an oxidative microenvironment; to minimize the damage, the isoaspartate residues can be 'repaired' by a specific L-isoaspartate (D-aspartate) protein O-methyltransferase (PIMT). As both premature aging and chronic oxidative stress are typical features of Down's syndrome (DS), we tested the hypothesis that deamidated proteins may build up in trisomic patients. Blood samples were obtained from children with karyotypically confirmed full trisomy 21 and from age-matched healthy controls.

Resveratrol: from basic science to the clinic.

Plants produce an extraordinary array of low molecular mass natural products endowed with biological activity. Among these molecules, resveratrol (3,5,4'-trihydroxystilbene) has been identified as an inhibitor of carcinogenesis with a pleiotropic mode of action. Extensive literature on its anticancer activity, performed in cellular models, suggests a potential antiproliferative and apoptogenic use of the stilbene.

Matrix metalloproteinases and their inhibitors as biomarkers for metal toxicity in vitro.

Exposure to nickel and chromium, and their compounds, has been associated with adverse health effects. These metals are two human carcinogens whose pathogenesis involves active extracellular matrix degradation and remodelling. In this work we have compared the effects of in vitro exposure to nickel and chromium of a keratinocyte cell line (HaCat).

Diverse effects of natural antioxidants on cyclosporin cytotoxicity in rat renal tubular cells.

Background: As is well known, the use of the immunosuppressive drug cyclosporin A (CsA) is partially restricted by its nephrotoxic effects, which include early changes in haemodynamics followed by irreversible injuries to the renal tubules. Although the mechanisms responsible for these side effects are poorly understood, an involvement of reactive oxygen species (ROS) has been suggested. In this study, we selected three natural antioxidants, resveratrol, hydroxytyrosol and vitamin E, on the basis of their scavenging capabilities, and tested their protective effects against CsA toxicity.

Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells.

Previous studies showed that long-wave ultraviolet (UVA) radiation induces severe skin damage through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. Recent results from our laboratory indicate a dramatic increase of both lipid peroxidation products (TBARS) and abnormal L-isoaspartyl residues, marker of protein damage, in UVA-irradiated human melanoma cells. In this study, the effects of hydroxytyrosol (DOPET), the major antioxidant compound present in olive oil, on UVA-induced cell damages, have been investigated, using a human melanoma cell line (M14) as a model system.

Plasma protein aspartyl damage is increased in hemodialysis patients: studies on causes and consequences.

Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage. This has been linked to the toxic effects of hyperhomocysteinemia in uremic erythrocytes; however, treatment aimed at abating homocysteine levels did not lead to significant reductions in plasma protein damage. The hypothesis that lack of reduction in protein damage could be due to protein increased intrinsic instability, as result of interference with the uremic milieu rather than to hyperhomocysteinemia, was put forward.

Oleuropein prevents oxidative myocardial injury induced by ischemia and reperfusion.

The potential protective effects of oleuropein, a dietary antioxidant of olive oil, has been investigated in the isolated rat heart. The organs were subjected to 30 minutes of no-flow global ischemia and then reperfused. At different time intervals, the coronary effluent was collected and assayed for creatine kinase activity as well as for reduced and oxidized glutathione.

Hyperhomocysteinemia and protein damage in chronic renal failure and kidney transplant pediatric patients--Italian initiative on uremic hyperhomocysteinemia (IIUH).

Background: Plasma homocysteine, a new cardiovascular risk factor in both children and adults, is higher in chronic renal failure or kidney transplant patients. This alteration has been linked, in chronic renal failure, to plasma protein damage, represented by increased L-isoaspartyl residues. We measured plasma homocysteine levels and plasma protein damage in pediatric patients from four different Italian regions with conservatively treated renal failure; hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), or transplants, to establish the presence of protein damage and the relative role of hyperhomocysteinemia.

Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia.

Background: Hyperhomocysteinaemia occurs in several genetically determined and acquired disorders and is highly prevalent in patients with uraemia. In these disorders, homocysteine precursor S-adenosylhomocysteine, a powerful competitive inhibitor of S-adenosylmethionine-dependent methyltransferases, is increased, suggesting unbalanced methylation. We aimed to investigate whether DNA hypomethylation is present in patients with uraemia who also have hyperhomocysteinaemia and whether regulation of specific classes of genes, dependent on DNA methylation, is compromised.

Protective effect of the phenolic fraction from virgin olive oils against oxidative stress in human cells.

This paper reports the protective effect of the phenolic fraction extracted from extra virgin olive oils (OOPEs) against the cytotoxic effects of reactive oxygen species in human erythrocytes and Caco-2 cells, employed as model systems. Pretreatment of cells with various OOPEs, indeed, provides a remarkable protection against oxidative damages: this effect was strictly dependent on the o-diphenolic content of the extracts. Moreover, the protective effects observable in cellular systems were compared with in vitro antioxidant properties, measured by using the FRAP (ferric reducing/antioxidant power) assay; the reducing ability of OOPEs strictly parallels their o-phenolic content.

Protein methylation as a marker of aspartate damage in glucose-6-phosphate dehydrogenase-deficient erythrocytes: role of oxidative stress.

The 'Mediterranean' variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency is due to the C563CT point mutation, leading to replacement of Ser with Phe at position 188, resulting in acute haemolysis triggered by oxidants. Previous work has shown increased formation of altered aspartate residues in membrane proteins during cell ageing and in response to oxidative stress in normal erythrocytes. These abnormal residues are specifically recognized by the repair enzyme L-isoaspartate (d-aspartate) protein O-methyltransferase (PCMT; EC 2.