Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells
- 8 April 2004
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 92 (2), 351-360
- https://doi.org/10.1002/jcb.20069
Abstract
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. Oxidative damage of endothelial cells (EC) is considered to be a critical aspect of the atherosclerotic process. To further investigate the molecular mechanisms involved in the atherogenicity of homocysteinylated LDL, we studied the effect of interaction between Hcy-LDL and EC on cell oxidative damage, using human aortic endothelial cells (HAEC) as experimental model. Homocysteinylation of LDL was carried out by incubation of LDL, isolated from plasma of healthy normolipemic subjects, with HcyT (10–100 μM). In our experimental conditions, homocysteinylation treatment was not accompanied by oxidative damage of LDL. No modifications of apoprotein structure and physico-chemical properties were observed in Hcy-LDL with respect to control LDL (c-LDL), as evaluated using the intrinsic fluorescence of tryptophan and the probe Laurdan incorporated in lipoproteins. Our results demonstrated that Hcy-LDL incubated at 37°C for 3 h with HAEC, induced an oxidative damage on human EC with a significant increase of lipid hydroperoxides in cells incubated with Hcy-LDL with respect to cell incubated with c-LDL. The compositional changes were associated with a significant decrease viability in cells treated with Hcy-LDL. The relationship between the levels of –SH groups of LDL and the oxidative damage of HAEC has been demonstrated. These results suggest that Hcy-LDL exert a cytotoxic effect that is likely related to an increase in lipid peroxidation and oxidative damage of EC.Keywords
This publication has 38 references indexed in Scilit:
- Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitusClinica Chimica Acta; International Journal of Clinical Chemistry, 2002
- Homocysteine Is a Protein Amino Acid in HumansPublished by Elsevier BV ,2002
- Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL−Free Radical Biology & Medicine, 2001
- Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells.JCI Insight, 1995
- Lipid peroxidation and susceptibility of low‐density lipoprotein to in vitro oxidation in hyperhomocysteinaemiaEuropean Journal of Clinical Investigation, 1995
- Atherosclerosis and glycationBioEssays, 1994
- Thiolation of low-density lipoproteins and their interaction with L2C leukemic lymphocytesBiochimie, 1986
- Superoxide‐dependent formation of hydroxyl radicals in the presence of thiol compoundsFEBS Letters, 1982
- Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis.JCI Insight, 1976