1,721,078 research outputs found

    Protective effect of paraoxonase activity in high-density lipoproteins against erythrocyte membranes peroxidation: a comparison between healthy subjects and type 1 diabetic patients

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    J Clin Endocrinol Metab. 2004 Jun;89(6):2957-62. Protective effect of paraoxonase activity in high-density lipoproteins against erythrocyte membranes peroxidation: a comparison between healthy subjects and type 1 diabetic patients. Ferretti G, Bacchetti T, Busni D, Rabini RA, Curatola G. SourceInstituto di Biochimica, Università Politecnica delle Marche, I-60131 Ancona, Italy. Abstract High-density lipoproteins (HDL) plays a key role in the protection against oxidative damage of lipoprotein and biological membranes. The aim of the present study was to investigate the relationship between the antioxidant role of HDL and the HDL-paraoxonase (PON) activity in healthy subjects and in type 1 diabetic patients. Moreover, the ability of HDL of controls and diabetic patients to protect and/or repair biological membranes from oxidative damage was studied. HDL were isolated from 31 type 1 diabetic patients and 31 sex- and age-matched healthy subjects and immediately used to evaluate lipid hydroperoxides and HDL-PON activity. Erythrocyte membranes obtained from healthy subjects were oxidized with 2,2-azo-bis(2-aminidinopropane)dihydrochloride and then incubated in the presence of HDL isolated from healthy or type 1 diabetic subjects, with measurements of membrane lipid hydroperoxides before and after the incubation. HDL from type 1 diabetic patients showed higher levels of lipid hydroperoxides and a lower activity of HDL-PON than healthy subjects. Moreover, HDL of type 1 diabetic patients protected less efficiently erythrocyte membranes against oxidative damage compared with HDL from healthy subjects. A negative correlation was found between HDL-PON activity and the levels of hydroperoxides of HDL, confirming the relationship between PON and lipid peroxidation and suggesting that subjects with low PON activity are more exposed to oxidative damage than subjects with high PON activity. The ability of HDL to protect erythrocyte membranes was positively correlated with HDL-PON activity and negatively correlated with the levels of lipid hydroperoxides of HDL of healthy subjects. These results confirm a linkage between PON activity and lipid peroxidation of lipoproteins and suggest that the ability of HDL to protect erythrocyte membranes might be related to the PON activity. It might be hypothesized that the decrease of PON activity in diabetic patients and the lower HDL protective action against membrane peroxidation could contribute to acceleration of arteriosclerosis in type 1 diabetes mellitus. PMID:15181084[PubMed - indexed for MEDLINE

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

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    Free Radic Biol Med. 2006 Oct 1;41(7):1031-40. Epub 2006 Jul 12. Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells. Negre-Salvayre A, Dousset N, Ferretti G, Bacchetti T, Curatola G, Salvayre R. SourceINSERM U 466, Hôpital Rangueil Toulouse, France. [email protected] Abstract 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. The antioxidant ability of HDL is due to the apoprotein moiety and to the presence of associated enzymes, paraoxonase and PAF-Acetyl Hydrolase. HDL prevent the intracellular oxidative stress and the inflammatory response elicited by oxidized LDL (ox-LDL), by inhibiting the NFkappaB signalling pathway, and the subsequent inflammatory events (expression of adhesion molecules, recruitment and proliferation of mononuclear cells within the vascular wall). HDL prevent ox-LDL-mediated cell activation and proliferation, this being also attributed to the presence in HDL of sphingosine-1 phosphate which modulates the migration and survival of vascular cells. Lastly, HDL inhibit apoptosis elicited by ox-LDL in vascular cells. Recent evidences indicate that, beside their strong antiatherogenic properties, HDL could exert their protective effect in diseases generally associated to inflammatory events. PMID:16962927[PubMed - indexed for MEDLINE

    Structural modifications of HDL and functional consequences

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    Atherosclerosis. 2006 Jan;184(1):1-7. Epub 2005 Sep 12. Structural modifications of HDL and functional consequences. Ferretti G, Bacchetti T, Nègre-Salvayre A, Salvayre R, Dousset N, Curatola G. SourceInstitute of Biochemistry, Faculty of Medicine, University of Ancona, via Ranieri 1-60131, Italy. [email protected] Abstract 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. The formation of lipid peroxidation derivatives, such as thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and aldehydes, is associated with changes of physical properties (fluidity, molecular order) and of apoprotein conformation. Non-enzymatic glycation, generally associated with lipoxidation, leads to form irreversible complexes called advanced glycation end products. These HDL modifications are accompanied with altered biological activities of HDL and associated enzymes, including paraoxonase, CETP and LCAT. Homocysteine-induced modification of HDL is mediated by homocysteine-thiolactone, and can be prevented by a calcium-dependent thiolactonase/paraoxonase. Tyrosylation of HDL induces the formation of dimers and trimers of apo AI, and alters cholesterol efflux. Phospholipases and proteolytic enzymes can also modify HDL lipid and apoprotein structure. HDL modification induces generally the loss of their anti-inflammatory and cytoprotective properties. This could play a role in the pathogenesis of atherosclerosis and neurodegenerative diseases such as Alzheimer's disease. PMID:16157342[PubMed - indexed for MEDLINE
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