Vitamin C and E prevent lipopolysaccharide-induced apoptosis in human endothelial cells by modulation of Bcl-2 and Bax.
Lipopolysaccharide induced apoptosis and necrosis of human umbilical venous endothelial cells in a time-dependent manner. Lipopolysaccharide (1 microgram/ml)-induced apoptosis was maximal after 18 h, whereas necrosis occurred after prolonged incubation for more than 24 h. The increase in apoptosis correlated with a reduction in Bcl-2, a potent cell death inhibitor. Furthermore, lipopolysaccharide treatment upregulated Bax, which heterodimerizes with and thereby inhibits Bcl-2. Both the antioxidant N-acetylcysteine and the combination of vitamin C and E (10 microM) completely inhibited lipopolysaccharide-induced apoptosis, whereas vitamin C or E alone was less effective. The reduction of lipopolysaccharide-induced apoptosis by vitamin C and E was paralleled by an increase in Bcl-2 and a decrease in Bax protein levels. Thus, vitamin C and E seem to interfere with the Bcl-2 family of apoptosis regulators in human umbilical venous endothelial cells.
Haendeler
J
J
Department of Internal Medicine IV, Johann Wolfgang Goethe-University Frankfurt, Germany.
Zeiher
A M
AM
Dimmeler
S
S
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
D000975:Antioxidants; C494826:BAX protein, human; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014810:Vitamin E; D001205:Ascorbic Acid; D000111:Acetylcysteine