Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells.

Beside their key role in the regulation of cholesterol homeostasis, HDL exhibit antioxidant and anti-inflammatory properties that participate to their general antiatherogenic effect. The purpose of this review is to summarize the recent findings on antioxidant activity and cytoprotective cell signalling elicited by HDL against oxidized LDL and proatherogenic agents in vascular cells. HDL exhibit an antioxidant activity efficient to prevent LDL oxidation, or to inactivate newly formed lipid oxidation products.

Structural modifications of HDL and functional consequences.

High density lipoproteins (HDL) are susceptible to structural modifications mediated by various mechanisms including oxidation, glycation, homocysteinylation or enzymatic degradation. Structural alterations of HDL may affect their functional and atheroprotective properties. Oxidants, such as hypochlorous acid, peroxyl radicals, metal ions, peroxynitrite, lipoxygenases and smoke extracts, can alter both surface and core components of HDL.

Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells.

Homocysteine-thiolactone (HcyT) is a toxic product whose synthesis is directly proportional to plasma homocysteine (Hcy) levels. Previous studies demonstrated that the interaction between HcyT and low density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL). Structural and functional alterations of Hcy-LDL have been described and it has been suggested that homocysteinylation could increase atherogenicity of LDL.

Copper-induced oxidative damage on astrocytes: protective effect exerted by human high density lipoproteins.

In the present study, we confirmed that copper ions induce oxidative damage in human astrocytes in culture, as demonstrated by the significant increase in the levels of hydroperoxides and in the fluorescence intensity of the fluorescent probe dichloro-dihydrofluorescein diacetate (H(2)DCFDA). The compositional changes were associated with a significant decrease in cell viability in astrocytes treated with 10 microM Cu(++) with respect to control cells. Astrocytes incubated with copper ions in the presence of high density lipoproteins (HDL) isolated from plasma of normolipemic subjects showed lower levels of hydroperoxides and a higher cell viability with respect to cells oxidized alone.

Protective effect of human HDL against Cu(2+)-induced oxidation of astrocytes.

Several studies support the role of copper-mediated oxidative injury in the development of neurodegenerative diseases. In this study we demonstrated that copper exerts an oxidant effect on cultured astrocytes as shown by the significant increase in the levels of hydroperoxides in astrocytes oxidized with 10 micromol/L Cu2+ for 4 h with respect to control cells. Using the fluorescent probe 2,7-dichloro-dihydrofluorescein diacetate (H2DCFDA) that represents an useful approach for measuring the production of reactive oxygen species (ROS), a significant increase in fluorescence intensity was observed in Cu(2+)-oxidized cells.

Acidic and neutral sialidase in the erythrocyte membrane of type 2 diabetic patients.

The behavior of the 2 sialidase forms present in the erythrocyte membrane was investigated in 117 subjects with type 2 diabetes mellitus versus 95 healthy controls. A significant increase of the acidic form of sialidase, which is anchored to the membrane by a glycosylphosphatidylinositol bridge, was observed in erythrocyte resealed membranes. On the contrary, the neutral form of the enzyme, the only one capable of removing lipid- and protein-bound sialic acid from endogenous and exogenous sialoderivatives, was significantly reduced with a consequent increase of erythrocyte membrane total sialic acid content.