0000000000288855
AUTHOR
Laurence Gesquière
Oxidant stress: the role of nutrients in cell-lipoprotein interactions
Oxidant stress is increasingly becoming an important hypothesis to explain the genesis of several pathologies, including cancer, atherosclerosis and also ageing. Beside a few rare genetic defects, dietary factors are thought to play a key role in the regulation of the production of reactive oxygenated species. An imbalance between nutrients, and in particular those involved in antioxidant status, could explain the onset of an enhanced production of free radicals. We will briefly review information concerning oxidation of lipids and lipoproteins which lead to atherothrombosis. We also present new findings supporting a role for blood platelets in generating oxidant species. New data are also …
Role of the cyclic AMP-dependent pathway in free radical-induced cholesterol accumulation in vascular smooth muscle cells.
We have previously reported that free radical-treated vascular smooth muscle cells (SMC) lead to cholesterol accumulation in vitro. In the current study, we investigated the effects of oxidative stress on cyclic AMP concentration and cAMP-dependent enzymes involved in cholesterol homeostasis in A7r5 cells. Under our conditions of a mild oxidative stress, namely with no change in cell viability, we found that free radicals, initiated using azobis-amidinopropane dihydrochloride (AAPH), resulted in a dose-dependent decrease in cellular cAMP which was opposed by vitamin E preincubation. Although the addition of adenylate cyclase activators (carbacyclin and forskolin) increased cAMP levels it di…
Determination of sterols, oxysterols, and fatty acids of phospholipids in cells and lipoproteins: A one-sample method
In addition to fatty acids, especially polyunsaturated species, cholesterol oxidizes and leads to various oxygenated derivatives, named oxysterols. They display a wide range of adverse biological properties. Monitoring oxysterols is important in the evaluation of the potential risks associated with lipid oxidation. In the present study, a quick and reliable method was developed for analysis of oxysterols, sterols, and fatty acid composition of phospholipids in the same biological sample. Total lipid extraction was determined after addition of several internal standards (epicoprostanol for sterols, 19-hydroxy-cholesterol for oxysterol and di-heptadecanoyl-phosphatidylcholine for phospholipid…
Impaired cellular cholesterol efflux by oxysterol-enriched high density lipoproteins.
One of the proposed antiatherogenicity role of high-density lipoproteins (HDL) is believed to stimulate removal of cholesterol from the peripheral cells back to the liver for excretion. We have investigated the effects of oxidation-related modifications of HDL on their ability to stimulate cholesterol efflux from cultured cells. Human HDL (HDL3, 1.13 < d < 1.21 g/ml) have been modified either by malondialdehyde or by copper-mediated oxidation (Ox-HDL3). Compared with native HDL3, the modified HDL3 resulted in a significantly reduced efflux of labeled cholesterol from preloaded macrophages (P388D1 cell line). Analysis of lipid composition of Ox-HDL3 by gas chromatography revealed the presenc…
Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells.
The transformation of macrophages and smooth muscle cells into foam cells by modified low-density lipoproteins (LDL) is one of the key events of atherogenesis. Effects of free radicals have mainly been studied in LDL, and other than toxicity, data dealing with direct action of free radicals on cells are scarce. This study focused on the direct effects of free radicals on cholesterol metabolism of smooth muscle cells. A free radical generator, azobis-amidinopropane dihydrochloride, was used, and conditions for a standardized oxidative stress were set up in vascular smooth muscle cells. After free radical action, the cells presented an accumulation of cholesterol that appeared to be the resul…