Protective effect of 17 beta-estradiol against the cytotoxicity of minimally oxidized LDL to cultured bovine aortic endothelial cells.
The ability of 17 beta-estradiol, progesterone, testosterone and cholesterol in preventing the cytotoxicity of oxidized LDL to cultured aortic bovine endothelial cells (BAEC) was tested and compared. The lipid peroxidation of LDL, promoted either by UV-C radiation, copper ions or cultured human lymphoblastoid cells, was inhibited in a dose-dependent manner by 17 beta-estradiol (IC50 were evaluated at around 50 +/- 10 mumol/l with UV on copper and 6 +/- 2 mumol/l with cells), whereas exogenous cholesterol, progesterone or testosterone were completely inactive under the range of concentrations tested (up to 100 mumol/l). Subsequently, this antioxidant effect of 17 beta-estradiol preventing LDL oxidation protected 'indirectly' BAEC against the cytotoxicity of oxidized LDL. 17 beta-Estradiol was also able to protect 'directly' BAEC against the cytotoxic effect of oxidized LDL (with an IC50 around 0.5 +/- 0.1 mumol/l), whereas the other steroids tested were almost completely inactive. This direct protective effect resulted from an increased resistance of BAEC against the cytotoxic effect of oxidized LDL as shown by pre-incubation of BAEC with 17 beta-estradiol. The protective effect of 17 beta-estradiol was present for 2-3 days. In conclusion, 17 beta-estradiol exhibited an antioxidant activity and was effective in protecting BAEC against the cytotoxicity of oxidized LDL by acting at two separate sites: (i) outside the cells, by inhibiting the LDL oxidation; (ii) inside the cells by increasing the cellular resistance against the cytotoxic effect of oxidized LDL. The potential relevance of these results in relation to prevention of atherogenesis is discussed.
Nègre-Salvayre
A
A
Department of Biochemistry, Faculty of Medicine, University Paul Sabatier, Toulouse, France.
Pieraggi
M T
MT
Mabile
L
L
Salvayre
R
R
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000648:ultrastructure; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D004875:Ergosterol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D010084:Oxidation-Reduction; D011374:Progesterone / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D008077:Lipoproteins, LDL; D014810:Vitamin E; D011374:Progesterone; D004958:Estradiol; D002784:Cholesterol; D004875:Ergosterol