Early involvement of ROS overproduction in apoptosis induced by 7-ketocholesterol.
Cholesterol oxidation products are increasingly considered as much more bioactive than the parent compound in the multifactor and multistep process that characterizes atherosclerosis. In particular, 7-ketocholesterol has been reported to induce oxidative stress as well as a marked pro-apoptotic effect in vascular cells including macrophages. With the aim to investigate a possible pathogenic correlation between the two events, cultivated murine macrophages were challenged with a concentration of 7-ketocholesterol actually detectable in human vasculature. Conclusive proof was obtained of a primary role of NADPH-oxidase in the overproduction of reactive oxygen species within cells treated with the oxysterol. In addition, such oxidative burst occurred very early after cell intoxication and it was definitely demonstrated as able to lead cells to apoptotic death. In fact, two metabolic inhibitors of NADPH-oxidase and the antioxidant epicatechin very well counteracted 7-ketocholesterol-induced apoptosis by preventing the oxysterol pro-oxidant action.
Leonarduzzi
Gabriella
G
Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Turin, Italy.
Vizio
Barbara
B
Sottero
Barbara
B
Verde
Veronica
V
Gamba
Paola
P
Mascia
Cinzia
C
Chiarpotto
Elena
E
Poli
Giuseppe
G
Biasi
Fiorella
F