Medizinische Universität Graz - Research portal
Selected Publication:
Monier, S; Samadi, M; Prunet, C; Denance, M; Laubriet, A; Athias, A; Berthier, A; Steinmetz, E; Jürgens, G; Nègre-Salvayre, A; Bessède, G; Lemaire-Ewing, S; Néel, D; Gambert, P; Lizard, G.
Impairment of the cytotoxic and oxidative activities of 7 beta-hydroxycholesterol and 7-ketocholesterol by esterification with oleate.
Biochem Biophys Res Commun. 2003; 303(3):814-824
Doi: 10.1016%2FS0006-291X%2803%2900412-1
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Jürgens Günther
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Atherosclerosis involves inflammatory processes, as well as cytotoxic and oxidative reactions. In atherosclerotic plaques, these phenomena are revealed by the presence of dead cells, oxidized lipids, and oxidative DNA damage, but the molecules triggering these events are still unknown. As 7 beta-hydroxycholesterol and 7-ketocholesterol, which are present at elevated concentrations in atherosclerotic lesions, are strongly cytotoxic and pro-oxidative, their effects were determined on cell death, superoxide anion and nitric oxide production, lipid peroxidation, and oxidative DNA damage. 7-Ketocholesterol- and 7 beta-hydroxycholesterol-induced cell death leads to a loss of mitochondrial potential, to increased permeability to propidium iodide, and to morphological nuclear changes (swelling, fragmentation, and/or condensation of nuclei). These effects are preceded by the formation of cytoplasmic monodansylcadaverine-positive structures and are associated with a rapid enhancement of cells overproducing superoxide anions, a decrease in cells producing nitric oxide, lipid peroxidation (formation of malondialdehyde and 4-hydroxynonenal adducts, low ratio of [unsaturated fatty acids]/[saturated fatty acids]) as well as oxidative DNA damage (8-oxoguanine formation). Noteworthy, none of the cytotoxic features previously observed with 7 beta-hydroxycholesterol and 7-ketocholesterol were noted with cholesterol, 7 beta-hydroxycholesteryl-3-oleate and 7-ketocholesteryl-3-oleate, with the exception of a slight increase in superoxide anion production with 7 beta-hydroxycholesteryl-3-oleate. This finding supports the theory that 7 beta-hydroxycholesterol and 7-ketocholesterol could induce cytotoxic and oxidative processes observed in atherosclerotic lesions and that esterification of these compounds may contribute to reducing atherosclerosis progression.
- Find related publications in this database (using NLM MeSH Indexing)
- Arteriosclerosis - etiology
- Cadaverine - analogs and derivatives
- Cell Survival - drug effects
- DNA Damage - drug effects
- Esterification - drug effects
- Humans - drug effects
- Hydroxycholesterols - chemistry
- Ketocholesterols - chemistry
- Lipid Peroxidation - drug effects
- Nitric Oxide - biosynthesis
- Oleic Acid - metabolism
- Oxidation-Reduction - metabolism
- Superoxides - metabolism
- U937 Cells - metabolism
- Find related publications in this database (Keywords)
- 7 beta-hydroxycholesterol
- 7-ketocholesterol
- 7 beta-hydroxycholesteryl-3-oleate
- 7-ketocholesteryl-3-oleate
- cholesterol
- apoptosis
- reactive oxygen species
- lipid peroxidation
- monodansylcadaverine
- 8-oxoguanine